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Weight-adjusted waist as an integrated index for fat, muscle and bone health in adults 体重调整后的腰围是成年人脂肪、肌肉和骨骼健康的综合指标。
IF 8.9 1区 医学
Journal of Cachexia, Sarcopenia and Muscle
Pub Date : 2023-08-07 DOI: 10.1002/jcsm.13302
Kyoung Jin Kim, Serhim Son, Kyeong Jin Kim, Sin Gon Kim, Nam Hoon Kim

Background

Unhealthy body composition, including high fat mass, low muscle mass and low bone mass, is a critical health issue in adults. The weight-adjusted waist index (WWI) estimates fat and muscle mass and may have implications for bone health. We examined its association with body composition outcomes in a large Korean adult cohort.

Methods

This study used data from the Korean National Health and Nutrition Examination Survey (2008–2011). WWI was calculated as waist circumference (cm) divided by the square root of body weight (kg). Dual-energy X-ray absorptiometry was used to measure bone mineral density (BMD), appendicular lean mass (ALM) and total body fat percentage. Unhealthy body composition was defined as combined presence of high fat mass, low bone mass and low muscle mass.

Results

A total of 5983 individuals (3034 men [50.7%] and 2949 women [49.3%]; mean age: 63.5 ± 8.7 years) were included. WWI was positively correlated with total body fat percentage (r = 0.478, P < 0.001) and inversely with ALM/weight (r = −0.485, P < 0.001) and BMD at the lumbar spine (r = −0.187, P < 0.001), femoral neck (r = −0.269, P < 0.001) and total hip (r = −0.255, P < 0.001). Higher WWI quartiles correlated with lower BMD, T-scores and ALM/weight, along with increased total body fat, evident in both genders and more pronounced in women, even after adjusting for confounders. This trend remained statistically significant across WWI quartiles for all analyses (P < 0.001). Higher WWI quartiles were also significantly associated with higher odds of unhealthy body composition, with adjusted odds ratio in the highest WWI group of 18.08 (95% CI, 4.32–75.61) in men and 6.36 (95% CI, 3.65–11.07) in women. The optimal cutoff values of WWI for unhealthy body composition were 10.4 cm/√kg in men and 10.5 cm/√kg in women.

Conclusions

In community-dwelling adults, high WWI values are associated with unfavourable body composition outcomes, indicating high fat mass, low muscle mass and low bone mass. WWI can potentially serve as an integrated index of body composition, underscoring the need for further research to validate its use in clinical settings.

背景：不健康的身体组成，包括高脂肪、低肌肉和低骨量，是成年人的一个关键健康问题。体重调整后的腰围指数（WWI）估计脂肪和肌肉质量，可能对骨骼健康有影响。我们在一个大型韩国成年队列中研究了它与身体成分结果的关系。方法：本研究使用了韩国国民健康和营养检查调查（2008-2011年）的数据。WWI计算为腰围（cm）除以体重（kg）的平方根。采用双能X线骨密度仪测量骨密度（BMD）、阑尾瘦块（ALM）和全身脂肪百分比。不健康的身体组成被定义为高脂肪、低骨量和低肌肉的综合存在。结果：共有5983人（3034名男性[507%]和2949名女性[49.3%]；平均年龄：63.5±8.7岁）被纳入。WWI与全身脂肪百分比呈正相关（r=0.478，P结论：在社区居住的成年人中，高WWI值与不利的身体成分结果有关，表明高脂肪量、低肌肉量和低骨量。WWI可以作为身体成分的综合指标，强调需要进一步研究来验证其在临床环境中的应用。
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引用次数: 0
Association of malignant ascites with systemic inflammation and muscle loss after treatment in advanced-stage ovarian cancer 晚期癌症治疗后恶性腹水与全身炎症和肌肉损失的相关性。
IF 8.9 1区 医学
Journal of Cachexia, Sarcopenia and Muscle
Pub Date : 2023-07-28 DOI: 10.1002/jcsm.13289
Chia-Sui Weng, Wan-Chun Huang, Chih-Long Chang, Ya-Ting Jan, Tze-Chien Chen, Jie Lee

Background

Malignant ascites is prevalent in advanced-stage ovarian cancer and may facilitate identification of the drivers of muscle loss. This study aimed to evaluate the association of ascites with changes in systemic inflammation and muscle after treatment of advanced-stage ovarian cancer.

Methods

We evaluated 307 patients with advanced-stage (III/IVA) ovarian cancer who underwent primary debulking surgery and adjuvant platinum-based chemotherapy between 2010 and 2019. The changes in skeletal muscle index (SMI) and radiodensity (SMD) were measured using pre-surgery and post-chemotherapy portal-venous phase contrast-enhanced computed tomography scans at L3. Systemic inflammation was measured using albumin levels, prognostic nutritional index (PNI), neutrophil-lymphocyte ratio (NLR), and platelet-lymphocyte ratio (PLR). Primary endpoint was the changes in SMI and SMD after treatment. Linear regression analysis was used to test associations between muscle change and other covariates. Mediation analysis was used to determine the mediator.

Results

The median (range) age was 53 (23–83) years. The median duration (range) of follow-up was 5.2 (1.1–11.3) years. Overall, 187 (60.9%) patients had ascites. The changes in muscle and systemic inflammatory markers after treatment were significantly different between patients with and without ascites (SMI: −3.9% vs. 2.2%, P < 0.001; SMD: −4.0% vs. −0.4%, P < 0.001; albumin: −4.4% vs. 2.1%, P < 0.001; PNI: −8.4% vs. −0.1%, P < 0.001; NLR: 20.6% vs. −29.4%, P < 0.001; and PLR: 1.7% vs. −19.4%, P < 0.001). The changes in SMI and SMD were correlated with the changes in albumin, PNI, NLR, and PLR (all P < 0.001). In multiple linear regression, ascites and NLR changes were negatively while albumin change was positively correlated with SMI change (ascites: β = −3.19, P < 0.001; NLR change: β = −0.02, P = 0.003; albumin change: β = 0.37, P < 0.001). Ascites and NLR changes were negatively while PNI change was positively correlated with SMD change (ascites: β = −1.28, P = 0.02; NLR change: β = −0.02, P < 0.001; PNI change: β = 0.11, P = 0.04). In mediation analysis, ascites had a direct effect on SMI change (P < 0.001) and an indirect effect mediated by NLR change (indirect effects = −1.61, 95% confidence interval [CI]: −2.22 to −1.08) and albumin change (indirect effects = −2.92, 95% CI: −4.01 to −1.94). Ascites had a direct effect on SMD change (P < 0.001) and an indirect eff

背景：恶性腹水在晚期癌症中普遍存在，可能有助于识别肌肉损失的驱动因素。本研究旨在评估晚期癌症治疗后腹水与全身炎症和肌肉变化的关系。方法：我们评估了307例癌症晚期（III/IVA）患者，他们在2010年至2019年间接受了初级减瘤手术和辅助铂基化疗。使用术前和化疗后L3的门静脉期对比增强计算机断层扫描测量骨骼肌指数（SMI）和放射密度（SMD）的变化。使用白蛋白水平、预后营养指数（PNI）、中性粒细胞淋巴细胞比率（NLR）和血小板淋巴细胞比率（PLR）测量全身炎症。主要终点是治疗后SMI和SMD的变化。线性回归分析用于检验肌肉变化和其他协变量之间的相关性。使用中介分析来确定调解员。结果：中位（范围）年龄为53岁（23-83岁）。随访的中位持续时间（范围）为5.2年（1.1-11.3）。总的来说，187名（60.9%）患者有腹水。有腹水和无腹水患者治疗后肌肉和全身炎症标志物的变化有显著差异（SMI:3.9%vs.2.2%，P结论：晚期卵巢癌症在初次减瘤手术和辅助化疗后，恶性腹水与全身炎症增强和肌肉损失有关。腹水与肌肉损失之间的联系可能是由全身炎症介导的。
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引用次数: 0
Comment on 'Hand grip strength-based cachexia index as a predictor of cancer cachexia and prognosis in patients with cancer' by Xie et al. Xie等人对“基于握力的恶病质指数作为癌症患者癌症恶病质和预后的预测指标”的评论。
IF 8.9 1区 医学
Journal of Cachexia, Sarcopenia and Muscle
Pub Date : 2023-07-28 DOI: 10.1002/jcsm.13298
Ping'an Ding, Jiaxiang Wu, Haotian Wu, Chenyu Sun, Muzi Meng, Scott Lowe, Yuan Tian, Honghai Guo, Lingjiao Meng, Qun Zhao

The study conducted by Xie et al.1 caught our attention, and we extend our gratitude for their valuable contribution. Measuring skeletal muscle index can be costly and tedious. Xie et al. proposed an alternative by using hand grip strength (HGS) to establish a new composite index, HGS-based cachexia index (CXI) (H-CXI), which is calculated as [HGS (kg)/height (m)2 × serum albumin (g/L)]/neutrophil-to-lymphocyte ratio. The H-CXI proved to be a rapid and accurate assessment tool, which can effectively evaluate the risk of cachexia and clinical outcome in cancer patients. The study revealed that H-CXI is independently associated with patient prognosis and is linked to age, pathological stage, systemic inflammation, and nutritional status. Low H-CXI was found to be an independent predictor of cachexia and prognosis in cancer patients. Moreover, H-CXI has shown to be a better prognosis evaluation tool for patients with the same pathological stage. In light of these findings, H-CXI is an economic and procedural advantage over the original CXI, is a comprehensive indicator, and is a multi-centre, prospective, large-sample study that provides reliable results. H-CXI has a reliable clinical effect and a broad clinical prospect in predicting prognosis and cancer cachexia.

It was found that the study analysed tumours of varying types with different pathological factors, potentially impacting the outcome. Additionally, the study lacked a prospective approach with rigorous inclusion criteria to evaluate the clinical applicability of H-CXI. Thus, a cohort study with registration number NCT01516944 was conducted to explore the clinical applicability of H-CIX as a predictor of cancer cachexia and prognosis among patients with locally advanced gastric cancer (LAGC). The study prospectively enrolled 290 LAGC patients who underwent direct radical surgical resection, of whom 111 (38.28%) had complete serologic and anthropometric data. The cohort primarily composed of males (62.16%) with a mean age of 58 years. Based on the optimal cut-off value for H-CXI from a previous study, 61 (54.95%) patients were categorized into the high H-CXI group and the remaining 50 (45.05%) into the low H-CXI group. During the follow-up period with a median duration of 64.9 months, 21 (18.92%) patients developed cancer cachexia, and patients in the high H-CXI group had a significantly lower risk of developing cancer cachexia than those in the low H-CXI group (11.48% vs. 28.00%, P = 0.027). Furthermore, patients in the high H-CXI group showed significantly better overall survival (OS) and disease-free survival (DFS) rates than those in the low H-CXI group (OS: 59.02% vs. 36.00%, P = 0.0043; DFS: 54.10% vs. 26.00%, P = 0.0024). Moreover, subgroup analysis revealed better 5-year OS and DFS rates for patients with high H-CXI at all pathological stages. Thus, the study found that H-CXI effectively predicted the prognosis and the risk of de

Xie et al.1的研究引起了我们的注意，我们对他们的宝贵贡献表示感谢。测量骨骼肌指数既昂贵又乏味。Xie等人提出了一种替代方法，利用手握力(HGS)建立新的复合指数——基于HGS的恶病质指数(CXI) (H-CXI)，计算方法为[HGS (kg)/身高(m)2 ×血清白蛋白(g/L)]/中性粒细胞与淋巴细胞比值。事实证明，H-CXI是一种快速准确的评估工具，可以有效地评估癌症患者恶病质的风险和临床结局。研究显示，H-CXI与患者预后独立相关，与年龄、病理分期、全身性炎症和营养状况有关。低H-CXI被发现是癌症患者恶病质和预后的独立预测因子。此外，H-CXI已被证明是同一病理分期患者更好的预后评估工具。根据这些发现，H-CXI在经济和程序上优于原始的CXI，是一个全面的指标，是一个多中心、前瞻性、大样本的研究，提供了可靠的结果。H-CXI在预测预后和肿瘤恶病质方面具有可靠的临床效果和广阔的临床前景。研究发现，该研究分析了具有不同病理因素的不同类型的肿瘤，这些因素可能会影响结果。此外，该研究缺乏前瞻性方法和严格的纳入标准来评估H-CXI的临床适用性。因此，我们开展了一项注册号为NCT01516944的队列研究，探讨H-CIX作为局部晚期胃癌(LAGC)患者癌症恶病质和预后预测因子的临床适用性。该研究前瞻性地招募了290例接受直接根治性手术切除的LAGC患者，其中111例(38.28%)具有完整的血清学和人体测量数据。该队列主要由男性(62.16%)组成，平均年龄58岁。根据既往研究中H-CXI的最佳临界值，61例(54.95%)患者被划分为高H-CXI组，其余50例(45.05%)患者被划分为低H-CXI组。在中位随访时间为64.9个月期间，21例(18.92%)患者发生癌症恶病质，高H-CXI组患者发生癌症恶病质的风险显著低于低H-CXI组(11.48% vs. 28.00%， P = 0.027)。此外，高H-CXI组患者的总生存率(OS)和无病生存率(DFS)明显优于低H-CXI组(OS: 59.02% vs. 36.00%， P = 0.0043;DFS: 54.10% vs. 26.00%， P = 0.0024)。此外，亚组分析显示，在所有病理阶段，高H-CXI患者的5年OS和DFS率都更高。因此，本研究发现H-CXI可有效预测LAGC患者的预后及发生恶性恶病质的风险，与前人研究结果一致。恶病质在癌症患者中普遍存在，并对其生活质量和治疗结果产生负面影响。2,3因此，鉴别生物标志物对于及时发现和评估发生恶病质的高危患者至关重要。一些研究已经证明CXI作为预测癌症患者预后的生物标志物的潜在功效。然而，CXI的实际应用受到相关成本和骨骼肌指数测试程序复杂性的限制。遗憾的是，最近开发CXI的研究一直处于停滞状态。幸运的是，H-CXI是一种有效预测癌症恶病质和预后的有用指标。除方便快捷外，还为TNM分期预后分层提供了有效补充。我们对谢等人的宝贵贡献表示感谢，并认识到他们的发现对相关领域的重要意义。H-CXI方法可以对患有恶病质的LAGC患者的肌肉、营养和炎症状况进行全面评估。该方法对患者的预后评估和个体化治疗具有重要的参考意义。我们对LAGC患者的队列研究表明，H-CXI在预测和评估LAGC患者恶病质和预后方面具有较高的准确性。H-CXI具有提高LAGC患者临床评价和治疗策略的潜力，最终有利于患者的生存(图1)。本研究得到河北省政府基金培养杰出人才项目(No. 2019012)的支持;河北省公共卫生委员会县级公立医院适宜卫生技术推广与储存项目(2019024);河北大学科技攻关计划项目(项目编号:8111111);ZD2019139)。
{"title":"Comment on 'Hand grip strength-based cachexia index as a predictor of cancer cachexia and prognosis in patients with cancer' by Xie et al.","authors":"Ping'an Ding,&nbsp;Jiaxiang Wu,&nbsp;Haotian Wu,&nbsp;Chenyu Sun,&nbsp;Muzi Meng,&nbsp;Scott Lowe,&nbsp;Yuan Tian,&nbsp;Honghai Guo,&nbsp;Lingjiao Meng,&nbsp;Qun Zhao","doi":"10.1002/jcsm.13298","DOIUrl":"10.1002/jcsm.13298","url":null,"abstract":"<p>The study conducted by Xie et al.<span><sup>1</sup></span> caught our attention, and we extend our gratitude for their valuable contribution. Measuring skeletal muscle index can be costly and tedious. Xie et al. proposed an alternative by using hand grip strength (HGS) to establish a new composite index, HGS-based cachexia index (CXI) (H-CXI), which is calculated as [HGS (kg)/height (m)2 × serum albumin (g/L)]/neutrophil-to-lymphocyte ratio. The H-CXI proved to be a rapid and accurate assessment tool, which can effectively evaluate the risk of cachexia and clinical outcome in cancer patients. The study revealed that H-CXI is independently associated with patient prognosis and is linked to age, pathological stage, systemic inflammation, and nutritional status. Low H-CXI was found to be an independent predictor of cachexia and prognosis in cancer patients. Moreover, H-CXI has shown to be a better prognosis evaluation tool for patients with the same pathological stage. In light of these findings, H-CXI is an economic and procedural advantage over the original CXI, is a comprehensive indicator, and is a multi-centre, prospective, large-sample study that provides reliable results. H-CXI has a reliable clinical effect and a broad clinical prospect in predicting prognosis and cancer cachexia.</p><p>It was found that the study analysed tumours of varying types with different pathological factors, potentially impacting the outcome. Additionally, the study lacked a prospective approach with rigorous inclusion criteria to evaluate the clinical applicability of H-CXI. Thus, a cohort study with registration number NCT01516944 was conducted to explore the clinical applicability of H-CIX as a predictor of cancer cachexia and prognosis among patients with locally advanced gastric cancer (LAGC). The study prospectively enrolled 290 LAGC patients who underwent direct radical surgical resection, of whom 111 (38.28%) had complete serologic and anthropometric data. The cohort primarily composed of males (62.16%) with a mean age of 58 years. Based on the optimal cut-off value for H-CXI from a previous study, 61 (54.95%) patients were categorized into the high H-CXI group and the remaining 50 (45.05%) into the low H-CXI group. During the follow-up period with a median duration of 64.9 months, 21 (18.92%) patients developed cancer cachexia, and patients in the high H-CXI group had a significantly lower risk of developing cancer cachexia than those in the low H-CXI group (11.48% vs. 28.00%, <i>P</i> = 0.027). Furthermore, patients in the high H-CXI group showed significantly better overall survival (OS) and disease-free survival (DFS) rates than those in the low H-CXI group (OS: 59.02% vs. 36.00%, <i>P</i> = 0.0043; DFS: 54.10% vs. 26.00%, <i>P</i> = 0.0024). Moreover, subgroup analysis revealed better 5-year OS and DFS rates for patients with high H-CXI at all pathological stages. Thus, the study found that H-CXI effectively predicted the prognosis and the risk of de","PeriodicalId":186,"journal":{"name":"Journal of Cachexia, Sarcopenia and Muscle","volume":"14 5","pages":"2449-2451"},"PeriodicalIF":8.9,"publicationDate":"2023-07-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jcsm.13298","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9883343","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}
引用次数: 1
Underweight status and development of end-stage kidney disease: A nationwide population-based study 终末期肾病的超重状况和发展：一项全国性的基于人群的研究。
IF 8.9 1区 医学
Journal of Cachexia, Sarcopenia and Muscle
Pub Date : 2023-07-28 DOI: 10.1002/jcsm.13297
Chang Seong Kim, Tae Ryom Oh, Sang Heon Suh, Hong Sang Choi, Eun Hui Bae, Seong Kwon Ma, Bongseong Kim, Kyung-Do Han, Soo Wan Kim

Background

Underweight status increases the risk of cardiovascular disease and mortality in the general population. However, whether underweight status is associated with an increased risk of developing end-stage kidney disease is unknown.

Methods

A total of 9 845 420 participants aged ≥20 years who underwent health checkups were identified from the Korean National Health Insurance Service database and analysed. Individuals with underweight (body mass index [BMI] < 18.5 kg/m2) and obesity (BMI ≥ 25 kg/m2) were categorized according to the World Health Organization recommendations for Asian populations.

Results

During a mean follow-up period of 9.2 ± 1.1 years, 26 406 participants were diagnosed with end-stage kidney disease. After fully adjusting for other potential predictors, the moderate to severe underweight group (<17 kg/m2) had a significantly higher risk of end-stage kidney disease than that of the reference (normal) weight group (adjusted hazard ratio, 1.563; 95% confidence interval, 1.337–1.828), and competing risk analysis to address the competing risk of death also showed the similar results (adjusted hazard ratio, 1.228; 95% confidence interval, 1.042–1.448). Compared with that of the reference BMI group (24–25 kg/m2), the adjusted hazard ratios for end-stage kidney disease increased as the BMI decreased by 1 kg/m2. In the sensitivity analysis, sustained underweight status or progression to underweight status over two repeated health checkups, when compared with normal weight status, had a higher hazard ratio for end-stage kidney disease.

Conclusions

Underweight status is associated with an increased risk of end-stage kidney disease, and this association gradually strengthens as BMI decreases.

背景：在普通人群中，体重不足会增加患心血管疾病和死亡的风险。然而，体重不足是否与发展为终末期肾病的风险增加有关尚不清楚。方法：从韩国国家健康保险服务数据库中确定并分析了9 845 420名年龄≥20岁接受健康检查的参与者。根据世界卫生组织针对亚洲人群的建议，对体重不足（体重指数[BMI]2）和肥胖（BMI≥25 kg/m2）的个体进行分类。结果：在9.2±1.1年的平均随访期内，26406名参与者被诊断为终末期肾病。在对其他潜在预测因素进行充分调整后，中度至重度体重不足组（2）患终末期肾病的风险显著高于参考（正常）体重组（调整后的危险比为1.563；95%置信区间为1.337-1.828），针对死亡竞争风险的竞争风险分析也显示出类似的结果（调整后的危险比为1.228；95%置信区间为1.042-1.448）。与参考BMI组（24-25 kg/m2）相比，终末期肾病的调整后危险比随着BMI降低1 kg/m2而增加。在敏感性分析中，与正常体重状态相比，持续的体重不足状态或在两次重复健康检查后发展为体重不足状态，对终末期肾病的风险比更高。结论：体重不足与终末期肾病的风险增加有关，并且这种联系随着BMI的降低而逐渐加强。
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引用次数: 0
Skeletal muscle-specific DJ-1 ablation-induced atrogenes expression and mitochondrial dysfunction contributing to muscular atrophy 骨骼肌特异性DJ-1消融诱导萎缩基因表达和线粒体功能障碍，导致肌肉萎缩。
IF 8.9 1区 医学
Journal of Cachexia, Sarcopenia and Muscle
Pub Date : 2023-07-19 DOI: 10.1002/jcsm.13290
Shuang Zhang, Hongmei Yan, Jiyang Ding, Ruwen Wang, Yonghao Feng, Xinyi Zhang, Xingyu Kong, Hongyu Gong, Xiaodan Lu, Alice Ma, Yinghui Hua, Huan Liu, Jiani Guo, Huanqing Gao, Zhenqi Zhou, Ru Wang, Peijie Chen, Tiemin Liu, Xingxing Kong

Background

DJ-1 is a causative gene for Parkinson's disease. DJ-1-deficient mice develop gait-associated progressive behavioural abnormalities and hypoactive forearm grip strength. However, underlying activity mechanisms are not fully explored.

Methods

Western blotting and quantitative real-time polymerase chain reaction approaches were adopted to analyse DJ-1 expression in skeletal muscle from aged humans or mice and compared with young subjects. Skeletal muscle-specific-DJ-1 knockout (MDKO) mice were generated, followed by an assessment of the physical activity phenotypes (grip strength, maximal load capacity, and hanging, rotarod, and exercise capacity tests) of the MDKO and control mice on the chow diet. Muscular atrophy phenotypes (cross-sectional area and fibre types) were determined by imaging and quantitative real-time polymerase chain reaction. Mitochondrial function and skeletal muscle morphology were evaluated by oxygen consumption rate and electron microscopy, respectively. Tail suspension was applied to address disuse atrophy. RNA-seq analysis was performed to indicate molecular changes in muscles with DJ-1 ablation. Dual-luciferase reporter assays were employed to identify the promoter region of Trim63 and Fbxo32 genes, which were indirectly regulated by DJ-1 via the FoxO1 pathway. Cytoplasmic and nuclear fractions of DJ-1-deleted muscle cells were analysed by western blotting. Compound 23 was administered into the gastrocnemius muscle to mimic the of DJ-1 deletion effects.

Results

DJ-1 expression decreased in atrophied muscles of aged human (young men, n = 2; old with aged men, n = 2; young women, n = 2; old with aged women, n = 2) and immobilization mice (n = 6, P < 0.01). MDKO mice exhibited no body weight difference compared with control mice on the chow diet (Flox, n = 8; MDKO, n = 9). DJ-1-deficient muscles were slightly dystrophic (Flox, n = 7; MDKO, n = 8; P < 0.05), with impaired physical activities and oxidative capacity (n = 8, P < 0.01). In disuse-atrophic conditions, MDKO mice showed smaller cross-sectional area (n = 5, P < 0.01) and more central nuclei than control mice (Flox, n = 7; MDKO, n = 6; P < 0.05), without alteration in muscle fibre types (Flox, n = 6; MDKO, n = 7). Biochemical analysis indicated that reduced mitochondrial function and upregulated of atrogenes induced these changes. Furthermore, RNA-seq analysis revealed enhanced activity of the FoxO

背景：DJ-1是帕金森病的致病基因。DJ-1缺陷小鼠出现步态相关的进行性行为异常和前臂握力低下。然而，潜在的活动机制尚未得到充分探索。方法：采用蛋白质印迹和实时定量聚合酶链反应方法分析DJ-1在老年人或小鼠骨骼肌中的表达，并与年轻人进行比较。产生骨骼肌特异性DJ-1敲除（MDKO）小鼠，然后评估MDKO和对照小鼠在饮食中的体力活动表型（握力、最大负荷能力以及悬吊、旋转杆和运动能力测试）。肌肉萎缩表型（横截面积和纤维类型）通过成像和定量实时聚合酶链式反应确定。线粒体功能和骨骼肌形态分别通过耗氧量和电子显微镜进行评估。采用尾部悬吊治疗废用性萎缩。进行RNA-seq分析以指示DJ-1消融后肌肉的分子变化。双荧光素酶报告基因测定用于鉴定Trim63和Fbxo32基因的启动子区，它们通过FoxO1途径被DJ-1间接调节。通过蛋白质印迹分析DJ-1缺失的肌肉细胞的细胞质和细胞核部分。将化合物23施用到腓肠肌中以模拟DJ-1缺失效应。结果：DJ-1在老年人（年轻男性，n=2；老年与老年男性，n=2；年轻女性，n=2，老年与老年女性，n=2）和固定小鼠萎缩肌肉中的表达降低（n=6，P结论：我们的研究结果阐明了骨骼肌DJ-1在调节机械刺激的分解代谢信号中的关键作用，为肌肉萎缩性疾病提供了治疗靶点。
{"title":"Skeletal muscle-specific DJ-1 ablation-induced atrogenes expression and mitochondrial dysfunction contributing to muscular atrophy","authors":"Shuang Zhang,&nbsp;Hongmei Yan,&nbsp;Jiyang Ding,&nbsp;Ruwen Wang,&nbsp;Yonghao Feng,&nbsp;Xinyi Zhang,&nbsp;Xingyu Kong,&nbsp;Hongyu Gong,&nbsp;Xiaodan Lu,&nbsp;Alice Ma,&nbsp;Yinghui Hua,&nbsp;Huan Liu,&nbsp;Jiani Guo,&nbsp;Huanqing Gao,&nbsp;Zhenqi Zhou,&nbsp;Ru Wang,&nbsp;Peijie Chen,&nbsp;Tiemin Liu,&nbsp;Xingxing Kong","doi":"10.1002/jcsm.13290","DOIUrl":"10.1002/jcsm.13290","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p><i>DJ-1</i> is a causative gene for Parkinson's disease. DJ-1-deficient mice develop gait-associated progressive behavioural abnormalities and hypoactive forearm grip strength. However, underlying activity mechanisms are not fully explored.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Western blotting and quantitative real-time polymerase chain reaction approaches were adopted to analyse DJ-1 expression in skeletal muscle from aged humans or mice and compared with young subjects. Skeletal muscle-specific-DJ-1 knockout (MDKO) mice were generated, followed by an assessment of the physical activity phenotypes (grip strength, maximal load capacity, and hanging, rotarod, and exercise capacity tests) of the MDKO and control mice on the chow diet. Muscular atrophy phenotypes (cross-sectional area and fibre types) were determined by imaging and quantitative real-time polymerase chain reaction. Mitochondrial function and skeletal muscle morphology were evaluated by oxygen consumption rate and electron microscopy, respectively. Tail suspension was applied to address disuse atrophy. RNA-seq analysis was performed to indicate molecular changes in muscles with DJ-1 ablation. Dual-luciferase reporter assays were employed to identify the promoter region of Trim63 and Fbxo32 genes, which were indirectly regulated by DJ-1 via the FoxO1 pathway. Cytoplasmic and nuclear fractions of DJ-1-deleted muscle cells were analysed by western blotting. Compound 23 was administered into the gastrocnemius muscle to mimic the of DJ-1 deletion effects.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>DJ-1 expression decreased in atrophied muscles of aged human (young men, <i>n</i> = 2; old with aged men, <i>n</i> = 2; young women, <i>n</i> = 2; old with aged women, <i>n</i> = 2) and immobilization mice (<i>n</i> = 6, <i>P</i> &lt; 0.01). MDKO mice exhibited no body weight difference compared with control mice on the chow diet (Flox, <i>n</i> = 8; MDKO, <i>n</i> = 9). DJ-1-deficient muscles were slightly dystrophic (Flox, <i>n</i> = 7; MDKO, <i>n</i> = 8; <i>P</i> &lt; 0.05), with impaired physical activities and oxidative capacity (<i>n</i> = 8, <i>P</i> &lt; 0.01). In disuse-atrophic conditions, MDKO mice showed smaller cross-sectional area (<i>n</i> = 5, <i>P</i> &lt; 0.01) and more central nuclei than control mice (Flox, <i>n</i> = 7; MDKO, <i>n</i> = 6; <i>P</i> &lt; 0.05), without alteration in muscle fibre types (Flox, <i>n</i> = 6; MDKO, <i>n</i> = 7). Biochemical analysis indicated that reduced mitochondrial function and upregulated of atrogenes induced these changes. Furthermore, RNA-seq analysis revealed enhanced activity of the FoxO","PeriodicalId":186,"journal":{"name":"Journal of Cachexia, Sarcopenia and Muscle","volume":"14 5","pages":"2126-2142"},"PeriodicalIF":8.9,"publicationDate":"2023-07-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jcsm.13290","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9828276","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}
引用次数: 1
Impaired proteostatic mechanisms other than decreased protein synthesis limit old skeletal muscle recovery after disuse atrophy 废用性萎缩后，除蛋白质合成减少外，蛋白稳定机制受损限制了老年骨骼肌的恢复。
IF 8.9 1区 医学
Journal of Cachexia, Sarcopenia and Muscle
Pub Date : 2023-07-14 DOI: 10.1002/jcsm.13285
Jordan D. Fuqua, Marcus M. Lawrence, Zachary R. Hettinger, Agnieszka K. Borowik, Parker L. Brecheen, Marcelina M. Szczygiel, Claire B. Abbott, Frederick F. Peelor III, Amy L. Confides, Michael Kinter, Sue C. Bodine, Esther E. Dupont-Versteegden, Benjamin F. Miller

Background

Skeletal muscle mass and strength diminish during periods of disuse but recover upon return to weight bearing in healthy adults but are incomplete in old muscle. Efforts to improve muscle recovery in older individuals commonly aim at increasing myofibrillar protein synthesis via mammalian target of rapamycin (mTOR) stimulation despite evidence demonstrating that old muscle has chronically elevated levels of mammalian target of rapamycin complex 1 (mTORC1) activity. We hypothesized that protein synthesis is higher in old muscle than adult muscle, which contributes to a proteostatic stress that impairs recovery.

Methods

We unloaded hindlimbs of adult (10-month) and old (28-month) F344BN rats for 14 days to induce atrophy, followed by reloading up to 60 days with deuterium oxide (D2O) labelling to study muscle regrowth and proteostasis.

Results

We found that old muscle has limited recovery of muscle mass during reloading despite having higher translational capacity and myofibrillar protein synthesis (0.029 k/day ± 0.002 vs. 0.039 k/day ± 0.002, P < 0.0001) than adult muscle. We showed that collagen protein synthesis was not different (0.005 k (1/day) ± 0.0005 vs. 0.004 k (1/day) ± 0.0005, P = 0.15) in old compared to adult, but old muscle had higher collagen concentration (4.5 μg/mg ± 1.2 vs. 9.8 μg/mg ± 0.96, P < 0.01), implying that collagen breakdown was slower in old muscle than adult muscle. This finding was supported by old muscle having more insoluble collagen (4.0 ± 1.1 vs. 9.2 ± 0.9, P < 0.01) and an accumulation of advanced glycation end products (1.0 ± 0.06 vs. 1.5 ± 0.08, P < 0.001) than adult muscle during reloading. Limited recovery of muscle mass during reloading is in part due to higher protein degradation (0.017 1/t ± 0.002 vs. 0.028 1/t ± 0.004, P < 0.05) and/or compromised proteostasis as evidenced by accumulation of ubiquitinated insoluble proteins (1.02 ± 0.06 vs. 1.22 ± 0.06, P < 0.05). Last, we showed that synthesis of individual proteins related to protein folding/refolding, protein degradation and neural-related biological processes was higher in old muscle during reloading than adult muscle.

Conclusions

Our data suggest that the failure of old muscle to recover after disuse is not due to limitations in the ability to synthesize myofibrillar proteins but bec

背景：骨骼肌的质量和力量在停用期间会减少，但在健康成年人恢复负重后会恢复，但在老年肌肉中是不完整的。改善老年人肌肉恢复的努力通常旨在通过哺乳动物雷帕霉素靶点（mTOR）刺激增加肌原纤维蛋白合成，尽管有证据表明老年肌肉的哺乳动物雷帕霉素靶点复合物1（mTORC1）活性水平长期升高。我们假设老年肌肉中的蛋白质合成高于成年肌肉，这会导致蛋白质静态应激，损害恢复。方法：我们卸载成年（10个月）和成年（28个月）F344BN大鼠的后肢14天以诱导萎缩，然后用氧化氘（D2O）标记重新加载长达60天以研究肌肉再生和蛋白稳定。结果：我们发现，尽管老年肌肉具有较高的翻译能力和肌原纤维蛋白合成，但在重新加载过程中，肌肉质量的恢复有限（0.029 k/天±0.002 vs.0.039 k/日±0.002，P结论：我们的数据表明，废用后老年肌肉未能恢复不是由于合成肌原纤维蛋白的能力受到限制，而是由于其他受损的蛋白稳定机制（如蛋白质折叠和降解）。这些数据提供了关于废弃后在蛋白质聚集体中积累的单个蛋白质的新信息，以及可能在受损恢复中发挥作用的某些生物过程，如蛋白质折叠和降解。因此，促进废用后旧肌肉再生的干预措施应针对已确定的受损蛋白稳定机制，而不是旨在增加蛋白质合成。
{"title":"Impaired proteostatic mechanisms other than decreased protein synthesis limit old skeletal muscle recovery after disuse atrophy","authors":"Jordan D. Fuqua,&nbsp;Marcus M. Lawrence,&nbsp;Zachary R. Hettinger,&nbsp;Agnieszka K. Borowik,&nbsp;Parker L. Brecheen,&nbsp;Marcelina M. Szczygiel,&nbsp;Claire B. Abbott,&nbsp;Frederick F. Peelor III,&nbsp;Amy L. Confides,&nbsp;Michael Kinter,&nbsp;Sue C. Bodine,&nbsp;Esther E. Dupont-Versteegden,&nbsp;Benjamin F. Miller","doi":"10.1002/jcsm.13285","DOIUrl":"10.1002/jcsm.13285","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Skeletal muscle mass and strength diminish during periods of disuse but recover upon return to weight bearing in healthy adults but are incomplete in old muscle. Efforts to improve muscle recovery in older individuals commonly aim at increasing myofibrillar protein synthesis via mammalian target of rapamycin (mTOR) stimulation despite evidence demonstrating that old muscle has chronically elevated levels of mammalian target of rapamycin complex 1 (mTORC1) activity. We hypothesized that protein synthesis is higher in old muscle than adult muscle, which contributes to a proteostatic stress that impairs recovery.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>We unloaded hindlimbs of adult (10-month) and old (28-month) F344BN rats for 14 days to induce atrophy, followed by reloading up to 60 days with deuterium oxide (D<sub>2</sub>O) labelling to study muscle regrowth and proteostasis.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>We found that old muscle has limited recovery of muscle mass during reloading despite having higher translational capacity and myofibrillar protein synthesis (0.029 <i>k</i>/day ± 0.002 vs. 0.039 <i>k</i>/day ± 0.002, <i>P</i> &lt; 0.0001) than adult muscle. We showed that collagen protein synthesis was not different (0.005 <i>k</i> (1/day) ± 0.0005 vs. 0.004 <i>k</i> (1/day) ± 0.0005, <i>P</i> = 0.15) in old compared to adult, but old muscle had higher collagen concentration (4.5 μg/mg ± 1.2 vs. 9.8 μg/mg ± 0.96, <i>P</i> &lt; 0.01), implying that collagen breakdown was slower in old muscle than adult muscle. This finding was supported by old muscle having more insoluble collagen (4.0 ± 1.1 vs. 9.2 ± 0.9, <i>P</i> &lt; 0.01) and an accumulation of advanced glycation end products (1.0 ± 0.06 vs. 1.5 ± 0.08, <i>P</i> &lt; 0.001) than adult muscle during reloading. Limited recovery of muscle mass during reloading is in part due to higher protein degradation (0.017 1/<i>t</i> ± 0.002 vs. 0.028 1/<i>t</i> ± 0.004, <i>P</i> &lt; 0.05) and/or compromised proteostasis as evidenced by accumulation of ubiquitinated insoluble proteins (1.02 ± 0.06 vs. 1.22 ± 0.06, <i>P</i> &lt; 0.05). Last, we showed that synthesis of individual proteins related to protein folding/refolding, protein degradation and neural-related biological processes was higher in old muscle during reloading than adult muscle.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>Our data suggest that the failure of old muscle to recover after disuse is not due to limitations in the ability to synthesize myofibrillar proteins but bec","PeriodicalId":186,"journal":{"name":"Journal of Cachexia, Sarcopenia and Muscle","volume":"14 5","pages":"2076-2089"},"PeriodicalIF":8.9,"publicationDate":"2023-07-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jcsm.13285","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9849279","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}
引用次数: 1
Associations between indoor air pollution for cooking and heating with muscle and sarcopenia in Chinese older population 中国老年人烹饪和取暖的室内空气污染与肌肉和少肌症的关系。
IF 8.9 1区 医学
Journal of Cachexia, Sarcopenia and Muscle
Pub Date : 2023-07-13 DOI: 10.1002/jcsm.13281
Zhigang Hu, Yufeng Tian, Xinyu Song, Fanjun Zeng, Ailan Yang

Background

Exposure to air pollution brings the advent effect for various diseases, but study about the relationship between air pollution and ageing is scant. We aimed to determine the associations between household air pollution for cooking and heating with muscle and sarcopenia in Chinese older population by a nationally representative study.

Methods

This cross-sectional study included individuals aged 60 and above from the China Health and Retirement Longitudinal Study between 2011 and 2015. The diagnosis of sarcopenia was defined by low muscle mass with low muscle strength and/or reduced physical performance. Generalized additive analyses and dose-dependent analyses with three models were used to assess the effects of different pattern of cooking and heating on muscle and sarcopenia.

Results

A total of 8126 Chinese older individuals with predominant male (53.7%) and mean age of 67.3 ± 6.0 years were included in our study. Solid fuel use in cooking showed significant declines in muscle strength (β = −0.424, 95% CI: −0.767, −0.082, P = 0.01 in model 3) and mass (β = −0.034, 95% CI: −0.051, −0.017, P < 0.01 in model 3), when compared with clean fuel use in cooking, respectively. Solid fuel for heating was correlated with lower muscle strength (β = −0.637, 95% CI: −1.033, −0.241, P < 0.01 in model 3) than clean fuel for heating. The joint use of solid fuel for cooking and heating was associated with reduced muscle strength (β = −0.835, 95% CI: −1.306, −0.365, P < 0.01 in model 3) and mass (β = −0.038, 95% CI: −0.061, −0.015, P < 0.01 in model 3) than clean fuel for cooking and heating. Solid fuel for cooking was associated with significantly increased risk of low muscle strength (adjusted OR = 1.29, 95% CI: 1.11, 1.50, P < 0.01 in model 3) and mass (adjusted OR = 1.35, 95% CI: 1.11, 1.61, P < 0.01 in model 3), possible sarcopenia (adjusted OR = 1.33, 95% CI: 1.19, 1.48, P < 0.01 in model 3) and sarcopenia (adjusted OR = 1.44, 95% CI: 1.21, 1.72, P < 0.01 in model 3) compared with clean fuel for cooking. Solid fuel for heating had a significant correlation with low muscle strength (adjusted OR = 1.30, 95% CI: 1.09, 1.56, P < 0.01 in model 3) and possible sarcopenia (adjusted OR = 1.49, 95% CI: 1.31, 1.70, P < 0.01 in model 3). Dose-dependent manner was shown in the associations between the number of solid fuel with low muscle strength and possible sarcopenia. Clean fuel for cooking and solid fuel for heating was positively associated with t

背景：暴露在空气污染中会导致各种疾病的出现，但关于空气污染与衰老之间关系的研究很少。我们旨在通过一项具有全国代表性的研究，确定中国老年人烹饪和取暖的家庭空气污染与肌肉和少肌症之间的关系。方法：这项横断面研究纳入了2011年至2015年间中国健康与退休纵向研究中60岁及以上的个体。肌肉减少症的诊断是指肌肉质量低、肌肉力量低和/或体力下降。使用三个模型的广义加性分析和剂量依赖性分析来评估不同烹饪和加热模式对肌肉和少肌症的影响。结果：本研究共纳入8126名中国老年人，其中男性占53.7%，平均年龄67.3±6.0岁。烹饪中固体燃料的使用显示出肌肉力量（模型3中的β=-0.424，95%CI:-0.767，-0.082，P=0.01）和质量（β=-0.034，95%CI:-0.051，-0.017，P）的显著下降。
{"title":"Associations between indoor air pollution for cooking and heating with muscle and sarcopenia in Chinese older population","authors":"Zhigang Hu,&nbsp;Yufeng Tian,&nbsp;Xinyu Song,&nbsp;Fanjun Zeng,&nbsp;Ailan Yang","doi":"10.1002/jcsm.13281","DOIUrl":"10.1002/jcsm.13281","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Exposure to air pollution brings the advent effect for various diseases, but study about the relationship between air pollution and ageing is scant. We aimed to determine the associations between household air pollution for cooking and heating with muscle and sarcopenia in Chinese older population by a nationally representative study.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>This cross-sectional study included individuals aged 60 and above from the China Health and Retirement Longitudinal Study between 2011 and 2015. The diagnosis of sarcopenia was defined by low muscle mass with low muscle strength and/or reduced physical performance. Generalized additive analyses and dose-dependent analyses with three models were used to assess the effects of different pattern of cooking and heating on muscle and sarcopenia.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>A total of 8126 Chinese older individuals with predominant male (53.7%) and mean age of 67.3 ± 6.0 years were included in our study. Solid fuel use in cooking showed significant declines in muscle strength (β = −0.424, 95% CI: −0.767, −0.082, <i>P</i> = 0.01 in model 3) and mass (β = −0.034, 95% CI: −0.051, −0.017, <i>P &lt;</i> 0.01 in model 3), when compared with clean fuel use in cooking, respectively. Solid fuel for heating was correlated with lower muscle strength (β = −0.637, 95% CI: −1.033, −0.241, <i>P</i> &lt; 0.01 in model 3) than clean fuel for heating. The joint use of solid fuel for cooking and heating was associated with reduced muscle strength (β = −0.835, 95% CI: −1.306, −0.365, <i>P &lt;</i> 0.01 in model 3) and mass (β = −0.038, 95% CI: −0.061, −0.015, <i>P</i> &lt; 0.01 in model 3) than clean fuel for cooking and heating. Solid fuel for cooking was associated with significantly increased risk of low muscle strength (adjusted OR = 1.29, 95% CI: 1.11, 1.50, <i>P</i> &lt; 0.01 in model 3) and mass (adjusted OR = 1.35, 95% CI: 1.11, 1.61, <i>P</i> &lt; 0.01 in model 3), possible sarcopenia (adjusted OR = 1.33, 95% CI: 1.19, 1.48, <i>P</i> &lt; 0.01 in model 3) and sarcopenia (adjusted OR = 1.44, 95% CI: 1.21, 1.72, <i>P</i> &lt; 0.01 in model 3) compared with clean fuel for cooking. Solid fuel for heating had a significant correlation with low muscle strength (adjusted OR = 1.30, 95% CI: 1.09, 1.56, <i>P</i> &lt; 0.01 in model 3) and possible sarcopenia (adjusted OR = 1.49, 95% CI: 1.31, 1.70, <i>P</i> &lt; 0.01 in model 3). Dose-dependent manner was shown in the associations between the number of solid fuel with low muscle strength and possible sarcopenia. Clean fuel for cooking and solid fuel for heating was positively associated with t","PeriodicalId":186,"journal":{"name":"Journal of Cachexia, Sarcopenia and Muscle","volume":"14 5","pages":"2029-2043"},"PeriodicalIF":8.9,"publicationDate":"2023-07-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jcsm.13281","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9776498","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}
引用次数: 2
Analysis of the rate of force development reveals high neuromuscular fatigability in elderly patients with chronic kidney disease 对力量发展率的分析显示，患有慢性肾脏疾病的老年患者具有较高的神经肌肉疲劳能力。
IF 8.9 1区 医学
Journal of Cachexia, Sarcopenia and Muscle
Pub Date : 2023-07-13 DOI: 10.1002/jcsm.13280
Antoine Chatrenet, Giorgina Piccoli, Jean Michel Audebrand, Massimo Torreggiani, Julien Barbieux, Charly Vaillant, Baptiste Morel, Sylvain Durand, Bruno Beaune

Background

Chronic kidney disease (CKD) induces muscle wasting and a reduction in the maximum voluntary force (MVF). Little is known about the neuromuscular fatigability in CKD patients, defined as the reduction of muscle force capacities during exercise. Neuromuscular fatigability is a crucial physical parameter of the daily living. The quantification of explosive force has been shown to be a sensitive means to assess neuromuscular fatigability. Thus, our study used explosive force estimates to assess neuromuscular fatigability in elderly CKD patients.

Methods

Inclusion criteria for CKD patients were age ≥ 60 years old and glomerular filtration rate (GFR) < 45 mL/min/1.73 m2 not on dialysis, and those for controls were GFR > 60 mL/min/1.73 m2, age and diabetes matched. The fatigability protocol focused on a handgrip task coupled with surface electromyography (sEMG). Scalars were extracted from the rate of force development (RFD): absolute and normalized time periods (50, 75, 100, 150 and 200 ms, RFD50, RFD75, RFD100, RFD150 and RFD200, respectively), peak RFD (RFDpeak in absolute; NRFDpeak normalized), time-to-peak RFD (t-RFDpeak) and the relative force at RFDpeak (MVF-RFDpeak). A statistical parametric mapping approach was performed on the force, impulse and RFD–time curves. The integrated sEMG with time at 0–30, 0–50, 0–100 and 0–200 ms time intervals relative to onset of sEMG activity was extracted and groups were compared separately for each sex.

Results

The cohort of 159 individuals had a median age of 69 (9IQR) years and body mass index was 27.6 (6.2IQR) kg/m2. Propensity-score-matched groups balanced CKD patients and controls by gender with 66 males and 34 females. In scalar analysis, CKD patients manifested a higher decrement than controls in the early phase of contraction, regarding the NRFDpeak (P = 0.009; η2p = 0.034) and RFD75 and RFD100 (for both P < 0.001; η2p = 0.068 and 0.064). The one-dimensional analysis confirmed that CKD males manifest higher and delayed neuromuscular fatigability, especially before 100 ms from onset of contraction. sEMG was lower in CKD patients than controls in the 0–100 ms (at rest: P = 0.049, Cohen's d = 0.458) and 0–200 ms (at rest: P = 0.016, Cohen's d = 0.496; during exercise: P = 0.006, Cohen's d = 

背景：慢性肾脏疾病（CKD）会导致肌肉萎缩和最大自主力（MVF）降低。对CKD患者的神经肌肉疲劳性知之甚少，其定义为运动过程中肌肉力量能力的降低。神经肌肉疲劳是日常生活中一个重要的生理参数。爆炸力的量化已被证明是评估神经肌肉疲劳能力的一种敏感手段。因此，我们的研究使用爆炸力估计来评估老年CKD患者的神经肌肉疲劳能力。方法：CKD患者的纳入标准为年龄≥60岁且肾小球滤过率（GFR）为2（未透析），对照组为GFR>60 mL/min/1.73 m2，年龄与糖尿病匹配。疲劳性方案侧重于抓握任务和表面肌电图（sEMG）。从力发展速率（RFD）中提取标量：绝对时间段和归一化时间段（分别为50、75、100、150和200ms、RFD50、RFD75、RFD100、RFD150和RFD200）、峰值RFD（RFDpeak为绝对值；NRFDpeak归一化）、达到峰值RFD的时间（t-RFDpeake）和RFD峰值处的相对力（MVF-RFDpeach）。对力、脉冲和RFD时间曲线进行了统计参数映射。提取相对于sEMG活性开始的0-30、0-50、0-100和0-200ms时间间隔的积分sEMG，并分别对每个性别的组进行比较。结果：159名患者的中位年龄为69岁（9IQR），体重指数为27.6（6.2IQR）kg/m2。倾向评分匹配组按性别平衡CKD患者和对照组，66名男性和34名女性。在标量分析中，CKD患者在收缩早期表现出比对照组更高的NRFDpeak下降率（P=0.009；η2p=0.034）、RFD75和RFD100（对于P2 P=0.068和0.064）。一维分析证实，CKD男性表现出更高和延迟的神经肌肉疲劳性，尤其是在收缩开始100 ms之前。CKD患者的sEMG在0-100毫秒（休息时：P=0.049，Cohen’s d=0.458）和0-200毫秒（静息时：P=0.016，Cohen‘s d=0.496；运动时：P=0.006，Cohen′s d=0.421）时间窗内低于对照组。对照组显示，在0-30ms（P=0.020，Cohen’s d=0.533）和0-50ms（P=0.010，Cohen‘s d=0.640）时间窗口内，sEMG的下降幅度大于CKD患者。与女性相反，男性在各组之间表现出几乎相同的差异。结论：我们的研究首次表明，CKD患者比对照组具有更高的疲劳性，这可能与运动单位募集受损有关，突出了CKD的神经驱动障碍。需要进一步的研究来证实这些发现。
{"title":"Analysis of the rate of force development reveals high neuromuscular fatigability in elderly patients with chronic kidney disease","authors":"Antoine Chatrenet,&nbsp;Giorgina Piccoli,&nbsp;Jean Michel Audebrand,&nbsp;Massimo Torreggiani,&nbsp;Julien Barbieux,&nbsp;Charly Vaillant,&nbsp;Baptiste Morel,&nbsp;Sylvain Durand,&nbsp;Bruno Beaune","doi":"10.1002/jcsm.13280","DOIUrl":"10.1002/jcsm.13280","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Chronic kidney disease (CKD) induces muscle wasting and a reduction in the maximum voluntary force (MVF). Little is known about the neuromuscular fatigability in CKD patients, defined as the reduction of muscle force capacities during exercise. Neuromuscular fatigability is a crucial physical parameter of the daily living. The quantification of explosive force has been shown to be a sensitive means to assess neuromuscular fatigability. Thus, our study used explosive force estimates to assess neuromuscular fatigability in elderly CKD patients.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Inclusion criteria for CKD patients were age ≥ 60 years old and glomerular filtration rate (GFR) &lt; 45 mL/min/1.73 m<sup>2</sup> not on dialysis, and those for controls were GFR &gt; 60 mL/min/1.73 m<sup>2</sup>, age and diabetes matched. The fatigability protocol focused on a handgrip task coupled with surface electromyography (sEMG). Scalars were extracted from the rate of force development (RFD): absolute and normalized time periods (50, 75, 100, 150 and 200 ms, RFD<sub>50</sub>, RFD<sub>75</sub>, RFD<sub>100</sub>, RFD<sub>150</sub> and RFD<sub>200</sub>, respectively), peak RFD (RFD<sub>peak</sub> in absolute; NRFD<sub>peak</sub> normalized), time-to-peak RFD (t-RFD<sub>peak</sub>) and the relative force at RFD<sub>peak</sub> (MVF-RFD<sub>peak</sub>). A statistical parametric mapping approach was performed on the force, impulse and RFD–time curves. The integrated sEMG with time at 0–30, 0–50, 0–100 and 0–200 ms time intervals relative to onset of sEMG activity was extracted and groups were compared separately for each sex.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>The cohort of 159 individuals had a median age of 69 (9<sub>IQR</sub>) years and body mass index was 27.6 (6.2<sub>IQR</sub>) kg/m<sup>2</sup>. Propensity-score-matched groups balanced CKD patients and controls by gender with 66 males and 34 females. In scalar analysis, CKD patients manifested a higher decrement than controls in the early phase of contraction, regarding the NRFD<sub>peak</sub> (<i>P</i> = 0.009; η<sup>2</sup><sub>p</sub> = 0.034) and RFD<sub>75</sub> and RFD<sub>100</sub> (for both <i>P</i> &lt; 0.001; η<sup>2</sup><sub>p</sub> = 0.068 and 0.064). The one-dimensional analysis confirmed that CKD males manifest higher and delayed neuromuscular fatigability, especially before 100 ms from onset of contraction. sEMG was lower in CKD patients than controls in the 0–100 ms (at rest: <i>P</i> = 0.049, Cohen's <i>d</i> = 0.458) and 0–200 ms (at rest: <i>P</i> = 0.016, Cohen's <i>d</i> = 0.496; during exercise: <i>P</i> = 0.006, Cohen's <i>d</i> = ","PeriodicalId":186,"journal":{"name":"Journal of Cachexia, Sarcopenia and Muscle","volume":"14 5","pages":"2016-2028"},"PeriodicalIF":8.9,"publicationDate":"2023-07-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jcsm.13280","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9829626","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}
引用次数: 1
Faecal microbiota transplantation from young rats attenuates age-related sarcopenia revealed by multiomics analysis 多组学分析显示，幼鼠粪便微生物群移植可减轻与年龄相关的少肌症。
IF 8.9 1区 医学
Journal of Cachexia, Sarcopenia and Muscle
Pub Date : 2023-07-13 DOI: 10.1002/jcsm.13294
Xiaoxing Mo, Lihui Shen, Ruijie Cheng, Pei Wang, Lin Wen, Yunhong Sun, Qiang Wang, Juan Chen, Shan Lin, Yuxiao Liao, Wei Yang, Hong Yan, Liegang Liu

Background

Gut microbiota plays a key role in the development of sarcopenia via the ‘gut-muscle’ axis, and probiotics-based therapy might be a strategy for sarcopenia. Fecal microbiota transplantation from young donors (yFMT) has attracted much attention because of its probiotic function. However, whether or not yFMT is effective for sarcopenia in old recipients is largely unknown. Thus, we aimed to investigate the effect and mechanism of yFMT on age-related sarcopenia.

Methods

The fecal microbiota of either young (12 weeks) or old (88 weeks) donor rats was transplanted into aged recipient rats for 8 weeks. Then, muscle mass, muscle strength, muscle function, muscle atrophy, and muscle regeneration capacity were measured. Analysis of fecal 16 s rRNA, serum non-targeted metabolomic, gut barrier integrity, and muscle transcriptome was conducted to elucidate the interaction between gut microbiota and skeletal muscles.

Results

As evaluated by magnetic resonance imaging examination, grip strength test (P < 0.01), rotarod test (P < 0.05), and exhaustive running test (P < 0.05), we found that yFMT mitigated muscle mass loss, muscle strength weakness, and muscle function impairment in aged rats. yFMT also countered age-related atrophy and poor regeneration capacity in fast- and slow-switch muscles, which were manifested by the decrease in slow-switch myofibres (both P < 0.01) and muscle interstitial fibrosis (both P < 0.05) and the increase in the cross-section area of myofibres (both P < 0.001), fast-switch myofibres (both P < 0.01), and muscle satellite cells (both P < 0.001). In addition, yFMT ameliorated age-related dysbiosis of gut microbiota and metabolites by promoting the production of beneficial bacteria and metabolites—Akkermansia, Lactococcus, Lactobacillus, γ-glutamyltyrosine, 3R-hydroxy-butanoic acid, and methoxyacetic acid and inhibiting the production of deleterious bacteria and metabolites—Family_XIII_AD3011_group, Collinsella, indoxyl sulfate, indole-3-carboxilic acid-O-sulphate, and trimethylamine N-oxide. Also, yFMT prevented age-related destruction of gut barrier integrity by increasing the density of goblet cells (P < 0.0001) and the expression levels of mucin-2 (P < 0.0001) and tight junctional proteins (all P < 0.05). Meanwhile, yFMT attenuated age-related impairment of mitochondrial biogenesis and function in fast- and slow-switch muscles. Correlation analysis revealed that yFMT-i

背景：肠道微生物群通过“肠道肌肉”轴在少肌症的发展中发挥着关键作用，基于益生菌的治疗可能是少肌症患者的一种策略。年轻供体粪便微生物群移植（yFMT）因其益生菌功能而备受关注。然而，yFMT是否对老年受试者的少肌症有效在很大程度上是未知的。因此，我们旨在研究yFMT对年龄相关性少肌症的影响和机制。方法：将青年（12周）或老年（88周）供体大鼠的粪便微生物群移植到老年受体大鼠体内，持续8周。然后，测量肌肉质量、肌肉力量、肌肉功能、肌肉萎缩和肌肉再生能力。对粪便16s rRNA、血清非靶向代谢组、肠道屏障完整性和肌肉转录组进行分析，以阐明肠道微生物群和骨骼肌之间的相互作用。结果：磁共振成像检查、握力测试（P结论：yFMT可重塑肠道微生物群和代谢产物的微生态失调，维持肠道屏障完整性，改善肌肉线粒体功能障碍，最终缓解老年大鼠少肌症。
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引用次数: 1
Corylifol A ameliorates muscle atrophy by inhibiting TAOK1/p38-MAPK/FoxO3 pathway in cancer cachexia Corylifol A通过抑制癌症恶病质中TAOK1/p38-MAPK/FoxO3途径改善肌肉萎缩。
IF 8.9 1区 医学
Journal of Cachexia, Sarcopenia and Muscle
Pub Date : 2023-07-13 DOI: 10.1002/jcsm.13288
Ruiqin Zhang, Qiang Shen, Yueping Wang, Xue Deng, Jialing Fan, Xiaofan Gu, Meng Fan, Kun Wei, Chun-Ru Cheng, Wei-Dong Zhang, Xiong-wen Zhang, Xuan Liu

Background

Corylifol A (CYA) is one of the main active components of Psoralea corylifolia L. CYA had been reported to have ameliorating effects on dexamethasone-induced atrophy of C2C12 mouse skeletal myotubes, but its effects on cancer cachexia were unclear. Here, we checked the influence of CYA on muscle atrophy in cancer cachexia mice and tried to clarify its mechanisms.

Methods

C26 tumour-bearing mice were applied as the animal model to examine the effects of CYA in attenuating cachexia symptoms. The in vitro cell models of TNF-α-induced C2C12 myotubes or ad-mRFP-GFP-LC3B-transfected C2C12 myotubes were used to check the influence of CYA on myotube atrophy based on both ubiquitin proteasome system (UPS) and autophagy-lysosome system. The possible direct targets of CYA were searched using the biotin-streptavidin pull-down assay and then confirmed using the Microscale thermophoresis binding assay. The levels of related signal proteins in both in vitro and in vivo experiments were examined using western blotting and immunocytochemical assay.

Results

The administration of CYA prevented body weight loss and muscle wasting in C26 tumour-bearing mice without affecting tumour growth. At the end of the experiment, the body weight of mice treated with 30 mg/kg of CYA (23.59 ± 0.94 g) was significantly higher than that of the C26 model group (21.66 ± 0.56 g) with P < 0.05. The values of gastrocnemius muscle weight/body weight of mice treated with 15 or 30 mg/kg CYA (0.53 ± 0.02% and 0.54 ± 0.01%, respectively) were both significantly higher than that of the C26 model group (0.45 ± 0.01%) with P < 0.01. CYA decreased both UPS-mediated protein degradation and autophagy in muscle tissues of C26 tumour-bearing mice as well as in C2C12 myotubes treated with TNF-α. The thousand-and-one amino acid kinase 1 (TAOK1) was found to be the direct binding target of CYA. CYA inhibited the activation of TAOK1 and its downstream p38-MAPK pathway thus decreased the level and nuclear location of FoxO3. siRNA knockdown of TAOK1 or regulation of the p38-MAPK pathway using activator or inhibitor could affect the ameliorating effects of CYA on myotube atrophy.

Conclusions

CYA ameliorates cancer cachexia muscle atrophy by decreasing both UPS degradation and autophagy. The ameliorating effects of CYA on muscle atrophy might be based on its binding with TAOK1 and inhibiting the TAOK1/p38-MAPK/FoxO3 pathway.

背景：CorylifolA（CYA）是补骨脂的主要活性成分之一。据报道，它对地塞米松诱导的C2C12小鼠骨骼肌管萎缩有改善作用，但对癌症恶病质的影响尚不清楚。在此，我们检测了CYA对癌症恶病质小鼠肌肉萎缩的影响，并试图阐明其机制。方法：以C26荷瘤小鼠为动物模型，观察CYA对恶病质症状的减轻作用。基于泛素-蛋白酶体系统（UPS）和自噬-溶酶体系统，使用TNF-α诱导的C2C12肌管或ad-mRFP-GFP-LC3B转染的C2C12-肌管的体外细胞模型来检测CYA对肌管萎缩的影响。使用生物素-链霉亲和素下拉测定法搜索CYA的可能直接靶标，然后使用微型热泳结合测定法确认。在体外和体内实验中，使用蛋白质印迹和免疫细胞化学分析检测相关信号蛋白的水平。结果：CYA的给药在不影响肿瘤生长的情况下防止了C26荷瘤小鼠的体重减轻和肌肉萎缩。实验结束时，30 mg/kg CYA治疗的小鼠体重（23.59±0.94 g）显著高于C26模型组（21.66±0.56 g），P＜0.01。结论：CYA通过减少UPS降解和自噬来改善癌症恶病质肌肉萎缩。CYA对肌肉萎缩的改善作用可能是基于其与TAOK1的结合和抑制TAOK1/p38 MAPK/FoxO3通路。
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