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Detection of Sarcopenia in Community-Dwelling Older Adults Using the SARC-F Questionnaire: Findings From the Southampton Longitudinal Study of Ageing (SaLSA) 使用SARC-F问卷检测社区居住老年人肌肉减少症：来自南安普顿老龄化纵向研究（SaLSA）的发现
JCSM rapid communications
Pub Date : 2024-09-28 DOI: 10.1002/rco2.108
Harnish P. Patel, Evie Boswell, Faidra Laskou, Leo D. Westbury, Gregorio Bevilacqua, Ilse Bloom, Cyrus Cooper, Pritti Aggarwal, Elaine M. Dennison

Aims

Sarcopenia is associated with substantial morbidity and mortality. The SARC-F self-rated questionnaire is a simple tool that can be rapidly implemented by clinicians to identify individuals with probable sarcopenia who may require further in-depth assessment. A score ≥ 4 is predictive of sarcopenia and poorer outcomes. We sought to identify the prevalence and demographic correlates of probable sarcopenia in a newly formed cohort of community-dwelling older adults.

Methods

A cross-sectional analysis of 480 participants (219 men and 261 women) identified from primary care in whom a questionnaire ascertaining demographic, lifestyle factors, comorbidities, nutrition risk and SARC-F score was completed between 2021 and 2022. Participant characteristics in relation to probable sarcopenia were examined using sex-stratified logistic regression. Age was included as a covariate.

Results

The median (lower quartile, upper quartile) age was 79.8 (76.9, 83.5) years. 12.8% (28) of men and 23% (60) of women had probable sarcopenia. Older age was associated with probable sarcopenia in both sexes (odds ratio [95% CI]: men 1.10 [1.02, 1.19], p = 0.01; women 1.08 [1.02, 1.14], p = 0.01) as was higher malnutrition risk score (men: 1.30 [1.12, 1.51], p = 0.001; women: 1.32 [1.17, 1.50], p < 0.001 per unit increase). Among men, being married or in a civil partnership or cohabiting was protective against probable sarcopenia (0.39 [0.17, 0.89], p = 0.03) as was reporting drinking any alcohol (0.34 [0.13, 0.92], p = 0.03), whereas in women generally similar relationships were seen though these were weaker. Higher BMI (1.14 (1.07, 1.22), p < 0.001 per unit increase) and more comorbidities (1.61 [1.34, 1.94], p < 0.001 per extra medical condition) were also associated with probable sarcopenia in women.

Conclusions

Probable sarcopenia (SARC-F score ≥ 4) was common in older adults living in their own homes. In addition to advancing age and malnutrition, socio-demographic factors were also important. Patients with a higher SARC-F and who are living with associated risk factors should be prioritised for further in-depth assessment for sarcopenia to allow the planning and implementation of interventions to mitigate potential adverse consequences.

目的肌少症与大量的发病率和死亡率相关。SARC-F自评问卷是一种简单的工具，临床医生可以快速实施，以识别可能需要进一步深入评估的肌肉减少症患者。评分≥4分可预测肌肉减少症和较差的预后。我们试图在一个新成立的社区居住老年人队列中确定可能的肌肉减少症的患病率和人口学相关性。方法对来自初级保健的480名参与者（219名男性和261名女性）进行横断面分析，这些参与者在2021年至2022年期间完成了问卷调查，确定了人口统计学、生活方式因素、合并症、营养风险和SARC-F评分。使用性别分层逻辑回归检查与可能的肌肉减少症相关的参与者特征。年龄是一个协变量。结果患者年龄中位数（上、下四分位数）为79.8岁（76.9岁、83.5岁）。12.8%（28）的男性和23%（60）的女性可能患有肌肉减少症。年龄较大可能与两性肌肉减少症相关(优势比[95% CI]：男性1.10 [1.02,1.19],p = 0.01；女性为1.08 [1.02,1.14],p = 0.01)，营养不良风险评分较高(男性为1.30 [1.12,1.51],p = 0.001；女性：每单位增加1.32 [1.17,1.50],p < 0.001)。在男性中，已婚或有民事伴侣关系或同居对可能的肌肉减少症有保护作用（0.39 [0.17,0.89],p = 0.03），报告饮酒（0.34 [0.13,0.92],p = 0.03），而在女性中，通常可以看到类似的关系，尽管这些关系较弱。较高的BMI（1.14(1.07, 1.22)，每单位增加p <； 0.001）和更多的合并症（1.61[1.34,1.94]，每额外医疗条件p <； 0.001）也与女性可能的肌肉减少症相关。结论：可能的肌肉减少症（SARC-F评分≥4）在独居的老年人中很常见。除了年龄增长和营养不良外，社会人口因素也很重要。对于SARC-F较高且存在相关危险因素的患者，应优先考虑进一步深入评估肌肉减少症，以便计划和实施干预措施以减轻潜在的不良后果。
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引用次数: 0
The Effect of Resistance Training on Markers of Cachexia in Patients with Heart Failure: A Systematic Review and Meta-Analysis 抗阻训练对心力衰竭患者恶病质标志物的影响：系统回顾和荟萃分析
JCSM rapid communications
Pub Date : 2024-09-23 DOI: 10.1002/rco2.104
Reina Hanania, Nephtali Marina, Brittany Cucchiaro, Adrian Slee
<div> <section> <h3> Background</h3> <p>Cachexia is a metabolic syndrome characterised by muscle wasting that is highly prevalent in subjects with heart failure (HF) and negatively affects physical function, quality of life, morbidity and mortality. Resistance training has been recently incorporated into cardiac rehabilitation exercise programmes to increase muscle strength in patients with HF. This systematic review and meta-analysis aim to assess the effects of resistance training on markers of cachexia in patients with HF.</p> </section> <section> <h3> Methods</h3> <p>Four electronic databases (MEDLINE, Embase, CENTRAL and CINAHL) were searched to identify randomised controlled trials (RCTs) evaluating the effects of resistance training-only programmes on published criteria for cachexia assessment including muscle strength, body composition (e.g. lean mass/muscle mass) or biochemical markers of cachexia (e.g. inflammatory markers) in patients with HF. Studies were selected based on pre-specified inclusion and exclusion criteria, with a risk of bias assessment carried out. Meta-analyses of muscle strength outcomes were completed using RevMan 5.4.1.</p> </section> <section> <h3> Results</h3> <p>Nine studies were included in this review. Pooled analysis of one repetition-maximum strength test of the lower [SMD 0.67 (95% Cl – 0.12, 1.22) <i>p</i>-value = 0.02] and upper extremities [SMD 1.20 (95% Cl – 0.62, 1.79) <i>p</i>-value <0.0001] showed a significant increase in muscle strength associated with resistance training, which are both important indicators of physical function. Resistance training did not increase muscle strength during rapid movements measured via peak torque at 60, 90 or 180°/s. There were no significant results recorded for changes in body composition and biochemical markers of cachexia. There were inconsistent findings for the effect of resistance training on quality of life. No studies reported findings on measures of anorexia or fatigue.</p> </section> <section> <h3> Conclusions</h3> <p>The findings of this review reveal the potential benefits of resistance training in preserving and enhancing muscle strength in patients with HF who are at risk of cardiac cachexia. Despite inconclusive results on body composition and quality of life, the inclusion of resistance training in cardiac rehabilitation guidelines has the potential to address issues of muscle weakness and frailty. Specific resistance training protocol recommendations to prevent or treat the development of cachexia cannot be made without the publication of more robu
恶病质是一种以肌肉萎缩为特征的代谢综合征，在心力衰竭（HF）患者中非常普遍，并对身体功能、生活质量、发病率和死亡率产生负面影响。阻力训练最近被纳入心脏康复训练计划，以增加心衰患者的肌肉力量。本系统综述和荟萃分析旨在评估抗阻训练对心衰患者恶病质标志物的影响。方法检索四个电子数据库（MEDLINE, Embase， CENTRAL和CINAHL），以确定随机对照试验（rct）评估仅阻力训练方案对已发表的恶病质评估标准的影响，包括心力衰竭患者的肌肉力量、身体成分（如瘦质量/肌肉质量）或恶病质生化标志物（如炎症标志物）。根据预先指定的纳入和排除标准选择研究，并进行偏倚风险评估。肌力结果的meta分析使用RevMan 5.4.1完成。结果本综述纳入9项研究。对下肢[SMD 0.67 (95% Cl - 0.12, 1.22) p值= 0.02]和上肢[SMD 1.20 (95% Cl - 0.62, 1.79) p值<；0.0001]的一次最大重复力量试验的汇总分析显示，阻力训练显著增加了肌肉力量，这两者都是身体功能的重要指标。阻力训练在快速运动中没有增加肌肉力量，通过峰值扭矩在60,90或180°/s测量。恶病质的体成分和生化指标没有明显的变化。关于抗阻训练对生活质量的影响，研究结果并不一致。没有研究报告厌食症或疲劳的测量结果。结论：本综述的研究结果揭示了阻力训练在保持和增强有心脏恶病质风险的心衰患者肌肉力量方面的潜在益处。尽管在身体组成和生活质量方面尚无定论，但在心脏康复指南中纳入阻力训练有可能解决肌肉无力和脆弱的问题。如果没有更有力的随机对照试验的发表，特别是对患有病毒质的心力衰竭患者进行检查，并仔细评估病毒质标志物的临床结果，就无法提出预防或治疗恶病质发展的具体阻力训练方案建议。
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引用次数: 0
Altered skeletal muscle density: a matter of increased fat infiltration or reduced muscle mass? 骨骼肌密度改变：是脂肪浸润增加还是肌肉质量减少？
JCSM rapid communications
Pub Date : 2024-06-25 DOI: 10.1002/rco2.98
Alex Martos Couto, Amauri Bomfim Junior, Guilherme Wesley Peixoto da Fonseca
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引用次数: 0
Long-term clinical, nutritional, and functional outcomes of COVID-19 patients after hospital discharge COVID-19患者出院后的长期临床、营养和功能结局
JCSM rapid communications
Pub Date : 2024-06-18 DOI: 10.1002/rco2.97
Laura Pedraza, Olga Laosa, Rocío Segovia-Moreno, Álvaro Alcalá, María Isabel Tornero-López, Germán Corral-Muñoz, Patricia López, Jose Antonio Carnicero, Maria Ramirez, Maria Camprubi, Leocadio Rodríguez-Mañas

Background

Long-term nutritional and functional status after hospitalization due to COVID-19 has been poorly described. We show the physical and nutritional stata and the symptoms compatible with Long-COVID in patients who survived after an episode of hospitalization due to COVID-19 and the associated factors.

Methods

Single-center prospective observational study. Clinical, nutritional, and physical function data were assessed in 345 subjects over 18 years of age hospitalized in an university hospital for a diagnosis of COVID-19 in 2020 at three different times of follow-up: 6 (n = 118), 9 (n = 115), and 15 months (n = 112) after discharge. All survivors discharged during each of those periods were called consecutively at the times of follow-up in order to collect data about their nutritional and functional stata, and long-COVID symptoms.

Results

The mean age of the 345 subjects included in the present study was 62.8 years (SD 15.8), and 180 (52.2%) were men. The mean number of comorbidities was 2.6 (SD 2.1). After a mean follow-up time of 10.2 ± 3.2 months, mean Barthel score showed a decrease of 2.00 (SD 0.12) points, that showed to be consistent disregarding the time after discharge (6 months: 1.71 ± 4.8; 9 months: 2.17 ± 5.97; 15 months: 2.20 ± 5.25). The risk factors associated with worsening in the Barthel index score were basal Barthel index [BI < 95; odds ratio (OR): 3.34, 95% confidence interval (CI): 1.26–8.85], age (OR: 1.03, CI: 1.00–1.06, per year), having comorbidities (≥3 pathologies) (OR: 1.98, CI: 1.00–3.90), and female sex (OR: 2.68, CI: 1.47–4.90). Self-reported Long-COVID symptoms were frequent, mainly those related to functioning: fatigue/tiredness (39.4%), decreased mobility (16.2%), and subjective loss of muscle mass/strength (15.9%) plus mental complaints (depression/anxiety; 20.6%). Decreased mobility (OR 7.82, CI: 3.69–16.55), cognitive impairment (OR 6.76, CI: 2.22–20.58) and a score in SARC-F ≥ 2 (OR: 3.89; CI: 2.03–7.49) at follow-up were associated to the worsening in BI. BMI showed a modest, non-significant decrease at 6 months (−0.3 ± 1.7 kg/m2), that was fully recovered in the longest follow-up period (+0.4 ± 2.1).

Conclusions

Admission for COVID-19 produces a significant functional loose, mainly in those who are older, female, and with a poor basal functional status and comorbidities. This impairment does not recover sp

背景 对 COVID-19 住院后的长期营养和功能状况的描述很少。我们展示了因 COVID-19 而住院治疗后存活的患者的身体和营养状况、符合 Long-COVID 的症状以及相关因素。 方法 单中心前瞻性观察研究。在出院后的 6 个月（118 人）、9 个月（115 人）和 15 个月（112 人）三个不同的随访时间，对 2020 年因诊断为 COVID-19 而在一家大学医院住院的 345 名 18 岁以上受试者的临床、营养和身体功能数据进行了评估。在上述每个时间段内出院的所有幸存者都会在随访时连续接到电话，以收集有关其营养和功能状况以及长期 COVID 症状的数据。 结果 本研究的 345 名受试者平均年龄为 62.8 岁（标准差为 15.8），其中 180 人（52.2%）为男性。合并症的平均数量为 2.6（标准差为 2.1）。平均随访时间为（10.2 ± 3.2）个月，平均 Barthel 评分下降了 2.00（SD 0.12）分，这与出院后的时间显示一致（6 个月：1.71 ± 4.8；9 个月：2.17 ± 5.97；15 个月：2.20 ± 5.25）。与 Barthel 指数评分恶化相关的风险因素包括基础 Barthel 指数[BI < 95; 赔率比（OR）：3.34，95% 置信区间（CI）：1.26-8.85]、年龄（OR：1.03，CI：1.00-1.06，每年）、合并症（≥3 种病症）（OR：1.98，CI：1.00-3.90）和女性（OR：2.68，CI：1.47-4.90）。自我报告的 Long-COVID 症状很常见，主要是与功能有关的症状：疲劳/疲倦（39.4%）、活动能力下降（16.2%）、主观肌肉质量/力量下降（15.9%）以及精神症状（抑郁/焦虑；20.6%）。随访时活动能力下降（OR：7.82；CI：3.69-16.55）、认知障碍（OR：6.76；CI：2.22-20.58）和 SARC-F 评分≥2（OR：3.89；CI：2.03-7.49）与 BI 的恶化有关。体重指数（BMI）在 6 个月时出现了适度的、非显著性的下降（-0.3 ± 1.7 kg/m2），但在最长的随访期内完全恢复（+0.4 ± 2.1）。 结论 COVID-19 的入院治疗会造成明显的功能障碍，主要发生在年龄较大、女性、基础功能状况较差和有合并症的患者身上。这种功能障碍不会自发恢复，是 COVID-19 长期症状的主要组成部分。
{"title":"Long-term clinical, nutritional, and functional outcomes of COVID-19 patients after hospital discharge","authors":"Laura Pedraza,&nbsp;Olga Laosa,&nbsp;Rocío Segovia-Moreno,&nbsp;Álvaro Alcalá,&nbsp;María Isabel Tornero-López,&nbsp;Germán Corral-Muñoz,&nbsp;Patricia López,&nbsp;Jose Antonio Carnicero,&nbsp;Maria Ramirez,&nbsp;Maria Camprubi,&nbsp;Leocadio Rodríguez-Mañas","doi":"10.1002/rco2.97","DOIUrl":"https://doi.org/10.1002/rco2.97","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Long-term nutritional and functional status after hospitalization due to COVID-19 has been poorly described. We show the physical and nutritional stata and the symptoms compatible with Long-COVID in patients who survived after an episode of hospitalization due to COVID-19 and the associated factors.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Single-center prospective observational study. Clinical, nutritional, and physical function data were assessed in 345 subjects over 18 years of age hospitalized in an university hospital for a diagnosis of COVID-19 in 2020 at three different times of follow-up: 6 (<i>n</i> = 118), 9 (<i>n</i> = 115), and 15 months (<i>n</i> = 112) after discharge. All survivors discharged during each of those periods were called consecutively at the times of follow-up in order to collect data about their nutritional and functional stata, and long-COVID symptoms.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>The mean age of the 345 subjects included in the present study was 62.8 years (<i>SD</i> 15.8), and 180 (52.2%) were men. The mean number of comorbidities was 2.6 (<i>SD</i> 2.1). After a mean follow-up time of 10.2 ± 3.2 months, mean Barthel score showed a decrease of 2.00 (<i>SD</i> 0.12) points, that showed to be consistent disregarding the time after discharge (6 months: 1.71 ± 4.8; 9 months: 2.17 ± 5.97; 15 months: 2.20 ± 5.25). The risk factors associated with worsening in the Barthel index score were basal Barthel index [BI &lt; 95; odds ratio (OR): 3.34, 95% confidence interval (CI): 1.26–8.85], age (OR: 1.03, CI: 1.00–1.06, per year), having comorbidities (≥3 pathologies) (OR: 1.98, CI: 1.00–3.90), and female sex (OR: 2.68, CI: 1.47–4.90). Self-reported Long-COVID symptoms were frequent, mainly those related to functioning: fatigue/tiredness (39.4%), decreased mobility (16.2%), and subjective loss of muscle mass/strength (15.9%) plus mental complaints (depression/anxiety; 20.6%). Decreased mobility (OR 7.82, CI: 3.69–16.55), cognitive impairment (OR 6.76, CI: 2.22–20.58) and a score in SARC-F ≥ 2 (OR: 3.89; CI: 2.03–7.49) at follow-up were associated to the worsening in BI. BMI showed a modest, non-significant decrease at 6 months (−0.3 ± 1.7 kg/m<sup>2</sup>), that was fully recovered in the longest follow-up period (+0.4 ± 2.1).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>Admission for COVID-19 produces a significant functional loose, mainly in those who are older, female, and with a poor basal functional status and comorbidities. This impairment does not recover sp","PeriodicalId":73544,"journal":{"name":"JCSM rapid communications","volume":"7 2","pages":"99-106"},"PeriodicalIF":0.0,"publicationDate":"2024-06-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/rco2.97","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143187059","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Myosteatosis and not low muscle mass is associated with lower survival in kidney transplant recipients 在肾移植受者中，肌骨增生和非低肌肉质量与较低的生存率相关
JCSM rapid communications
Pub Date : 2024-05-31 DOI: 10.1002/rco2.96
Kristoffer N.D. Huitfeldt Sola, Helena M. Genberg, Carla M. Avesani, Torkel B. Brismar

Background

Myosteatosis, that is muscle fat infiltration, is an important marker of muscle quality, affecting quality of life and survival in patients with chronic kidney disease (CKD). However, the connection between myosteatosis, skeletal muscle index (SMI) and survival in kidney transplant (KTx) recipients remains unclear.

Methods

This retrospective observational study included a cohort of consecutive adult kidney recipients transplanted between 2010 and 2017 in Stockholm. Preoperative abdominal computed tomography (CT) images obtained after diagnosis of CKD 5 and within 36 months of transplantation were collected. Using established criteria, we measured muscle area at the third lumbar vertebra (L3 level) and identified low attenuation muscle, indicating myosteatosis. Each area was divided by height squared providing the SMI, and fatty muscle index (FMI). Given that there is no commonly accepted definition of sarcopenia, two cut-offs for SMI were used to define low muscle mass, Cut-off 1 (≤32.8 for women and ≤44.7 for men) and Cut-off 2 (≤38.5 for women and ≤52.4 for men). Average radiodensity of skeletal muscle and Charlson comorbidity index were calculated for each patient. The influence on survival from SMI, FMI, SMI/FMI ratio, and radiodensity was analysed.

Results

Out of 582 KTx recipients, 266 (46%) had a pre-transplant abdominal CT available. Applying SMI Cut-off 1, 30 recipients (11%) had sarcopenia compared with 106 (40%) with Cut-off 2. Neither SMI nor FMI was associated with survival. Yet there was an association between SMI/FMI ratio and survival, patients with the lowest quintile SMI/FMI ratio having a significantly lower survival when compared with the highest quintile, both in the crude model and when adjusted for age, gender, and comorbidity. Additionally, FMI, radiodensity, and SMI/FMI, but not SMI, were significantly associated with Charlson comorbidity index (P < 0.01).

Conclusions

The SMI/FMI ratio may be associated with both pre-transplant comorbidity and post-transplant survival even though the significance of SMI is unclear. This suggests that SMI/FMI ratio is a better indicator of muscular impairment than skeletal muscle quantity alone. The finding may reflect the complex interplay between muscle mass, muscular fat infiltration and metabolic health, all important determinants of wellness and longevity. In summary, our study underscores the potential of the SMI/FMI ratio a

背景肌肥大症，即肌肉脂肪浸润，是肌肉质量的重要标志，影响慢性肾脏疾病（CKD）患者的生活质量和生存。然而，肾移植（KTx）受者骨骼肌指数（SMI）和存活之间的关系尚不清楚。方法：本回顾性观察性研究纳入了2010年至2017年在斯德哥尔摩连续移植的成人肾受体队列。收集CKD 5诊断后及移植36个月内术前腹部CT图像。使用既定标准，我们测量了第三腰椎（L3水平）的肌肉面积，并确定了低衰减肌肉，表明肌骨化症。每个区域除以身高的平方，给出SMI和脂肪肌肉指数（FMI）。鉴于肌少症没有一个普遍接受的定义，我们使用了SMI的两个临界值来定义低肌肉量，临界值1（女性≤32.8，男性≤44.7）和临界值2（女性≤38.5，男性≤52.4）。计算每位患者骨骼肌平均放射密度和Charlson合并症指数。分析SMI、FMI、SMI/FMI比值和放射密度对生存率的影响。结果在582例KTx受者中，266例（46%）有移植前腹部CT。应用SMI cut - t1, 30名接受者（11%）出现肌肉减少症，而cut - t2有106名接受者（40%）出现肌肉减少症。SMI和FMI都与生存无关。然而，在SMI/FMI比率和生存率之间存在关联，SMI/FMI比率最低的五分位数患者的生存率明显低于最高的五分位数，无论是在粗糙模型中还是在调整年龄、性别和合病后。此外，FMI、放射密度和SMI/FMI与Charlson合并症指数(P <；0.01)。结论SMI/FMI比值可能与移植前合并症和移植后生存有关，尽管SMI的意义尚不清楚。这表明SMI/FMI比值比单独的骨骼肌数量更能反映肌肉损伤。这一发现可能反映了肌肉质量、肌肉脂肪浸润和代谢健康之间复杂的相互作用，这些都是健康和长寿的重要决定因素。总之，我们的研究强调了SMI/FMI比率作为KTx后预后预测因子的潜力，这一发现可能适用于其他患者群体。
{"title":"Myosteatosis and not low muscle mass is associated with lower survival in kidney transplant recipients","authors":"Kristoffer N.D. Huitfeldt Sola,&nbsp;Helena M. Genberg,&nbsp;Carla M. Avesani,&nbsp;Torkel B. Brismar","doi":"10.1002/rco2.96","DOIUrl":"https://doi.org/10.1002/rco2.96","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Myosteatosis, that is muscle fat infiltration, is an important marker of muscle quality, affecting quality of life and survival in patients with chronic kidney disease (CKD). However, the connection between myosteatosis, skeletal muscle index (SMI) and survival in kidney transplant (KTx) recipients remains unclear.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>This retrospective observational study included a cohort of consecutive adult kidney recipients transplanted between 2010 and 2017 in Stockholm. Preoperative abdominal computed tomography (CT) images obtained after diagnosis of CKD 5 and within 36 months of transplantation were collected. Using established criteria, we measured muscle area at the third lumbar vertebra (L3 level) and identified low attenuation muscle, indicating myosteatosis. Each area was divided by height squared providing the SMI, and fatty muscle index (FMI). Given that there is no commonly accepted definition of sarcopenia, two cut-offs for SMI were used to define low muscle mass, Cut-off 1 (≤32.8 for women and ≤44.7 for men) and Cut-off 2 (≤38.5 for women and ≤52.4 for men). Average radiodensity of skeletal muscle and Charlson comorbidity index were calculated for each patient. The influence on survival from SMI, FMI, SMI/FMI ratio, and radiodensity was analysed.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Out of 582 KTx recipients, 266 (46%) had a pre-transplant abdominal CT available. Applying SMI Cut-off 1, 30 recipients (11%) had sarcopenia compared with 106 (40%) with Cut-off 2. Neither SMI nor FMI was associated with survival. Yet there was an association between SMI/FMI ratio and survival, patients with the lowest quintile SMI/FMI ratio having a significantly lower survival when compared with the highest quintile, both in the crude model and when adjusted for age, gender, and comorbidity. Additionally, FMI, radiodensity, and SMI/FMI, but not SMI, were significantly associated with Charlson comorbidity index (<i>P</i> &lt; 0.01).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>The SMI/FMI ratio may be associated with both pre-transplant comorbidity and post-transplant survival even though the significance of SMI is unclear. This suggests that SMI/FMI ratio is a better indicator of muscular impairment than skeletal muscle quantity alone. The finding may reflect the complex interplay between muscle mass, muscular fat infiltration and metabolic health, all important determinants of wellness and longevity. In summary, our study underscores the potential of the SMI/FMI ratio a","PeriodicalId":73544,"journal":{"name":"JCSM rapid communications","volume":"7 2","pages":"91-98"},"PeriodicalIF":0.0,"publicationDate":"2024-05-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/rco2.96","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143187337","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Cardiovascular and muscular plasticity in an endurance-master athlete following 12 weeks of detraining and retraining: a case study 一名耐力级运动员经过12周的去训练和再训练后的心血管和肌肉可塑性：一个案例研究
JCSM rapid communications
Pub Date : 2024-05-30 DOI: 10.1002/rco2.93
Nadège Zanou, Vincent Gremeaux, Nicolas Place, Romuald Lepers

Background

This study examined the cardiorespiratory and muscular adaptations of a 53-year-old endurance master athlete following 12 weeks of detraining and retraining.

Methods

Data were collected before and after detraining, and after retraining. Maximal oxygen uptake (VO2max) was evaluated during maximal cycling exercise. Proteins involved in muscle contraction, mitochondrial function and glycolysis were investigated using western blot analysis.

Results

VO2max decreased by 7% after detraining and was 5% greater than baseline after retraining. Detraining induced an important increase in the ryanodine receptor type 1 protein levels (RyR1, +44%) with a decrease in the protein levels of its stabilizer FKBP12 (−24%). We observed a 138% increase in the sarco-endoplasmic reticulum ATPase 1 protein and a 42% increase in the myosin heavy chain fast-twitch protein in response to detraining. This was associated with depressed levels of the mitochondrial biogenesis and oxidative phosphorylation (OXPHOS) proteins, while the expression of the mitochondrial dynamic proteins appeared stimulated. Twelve weeks of retraining reversed almost all the alterations observed in muscle proteins, but specifically increased mitochondrial biogenesis, OXPHOS and antioxidant defence proteins as well as the glucose transporter 4 (Glut-4, +36%) and hexokinase (+100%) proteins levels above the baseline. The mitochondrial dynamic proteins were further increased with the retraining.

Conclusions

These data provide novel information on cardiorespiratory and muscular plasticity, suggesting that highly endurance-trained athletes might show substantial muscular adaptations while retrained after a detraining period and call for more extensive clinical trials.

本研究检测了一名53岁的耐力级运动员在12周的去训练和再训练后的心肺和肌肉适应性。方法收集去训练前后和再训练前后的数据。最大摄氧量（VO2max）在最大循环运动中进行评估。蛋白参与肌肉收缩，线粒体功能和糖酵解用western blot分析。结果去训练后最大摄氧量下降7%，再训练后较基线提高5%。去训练诱导ryanodine受体1型蛋白水平（RyR1, +44%）显著增加，其稳定剂FKBP12蛋白水平下降（- 24%）。我们观察到肌内质网atp酶1蛋白增加138%，肌球蛋白重链快速收缩蛋白增加42%。这与线粒体生物发生和氧化磷酸化（OXPHOS）蛋白水平下降有关，而线粒体动态蛋白的表达则受到刺激。12周的再训练几乎逆转了肌肉蛋白中观察到的所有变化，但特别是线粒体生物发生、OXPHOS和抗氧化防御蛋白以及葡萄糖转运蛋白4（谷氨酸-4，+36%）和己糖激酶（+100%）蛋白水平高于基线水平。随着再训练，线粒体动态蛋白进一步增加。这些数据提供了关于心肺和肌肉可塑性的新信息，表明高耐力训练的运动员可能在去训练期后再训练时表现出大量的肌肉适应性，需要更广泛的临床试验。
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引用次数: 0
Uncorrected and subcutaneous fat-corrected echo intensities are similarly associated with magnetic resonance imaging per cent fat 未校正回波强度和皮下脂肪校正回波强度与磁共振成像脂肪百分比的关系相似
JCSM rapid communications
Pub Date : 2024-05-07 DOI: 10.1002/rco2.92
Benjamin Rush, Sujay Garlapati, Jevin Lortie, Katie Osterbauer, Timothy J. Colgan, Daiki Tamada, Toby C. Campbell, Anne Traynor, Ticiana Leal, Kenneth Lee, Scott B. Reeder, Adam J. Kuchnia

Background

Establishing interchangeable biomedical imaging-based measures to assess myosteatosis clinically may lead to the prevention of muscle wasting, yet neither a consensus measure nor a conversion between measures exists. Ultrasound echo intensity (EI) potentially assesses myosteatosis, but subcutaneous adipose tissue (SAT) thickness and user force application have been shown to influence EI. Although correction factors exist to adjust EI for SAT thickness, they are modelled against poor or no reference measures. Modelling EI corrections against a robust reference measure of myosteatosis, like magnetic resonance imaging (MRI)-based proton density fat fraction (PDFF), is necessary for EI's clinical application.

Methods

Healthy young adults, healthy older adults, and older adults undergoing treatment for lung cancer (n = 10 per group with 50% females) had PDFF and EI at 0, 5, 10, and 15 N measured on their right rectus femoris (RF). We compared EI, SAT thickness, and RF thickness between forces and groups and assessed the relationships between EI adjusted by four different correction factors and PDFF.

Results

The mean age of our sample was 48.63 ± 19.68 years and had a body mass index of 25.21 ± 5.19 kg/m2. The correlation between PDFF and raw EI was r = 0.59 (P < 0.001) with negligible increases by previously published correction factors (Young: 0.62, P < 0.001; Neto Müller: 0.61, P < 0.001). EI, SAT thickness, and RF thickness did not significantly differ between forces (χ2 = 0.31, P = 0.957; χ2 = 2.39, P = 0.496; and χ2 = 7.75, P = 0.051, respectively). EI and PDFF were significantly lower among young healthy adults compared with older adult groups (χ2 = 12.88, P = 0.002, and χ2 = 9.13, P = 0.010, respectively).

Conclusions

EI is correlated with PDFF regardless of force with no improvement from previously published correction factors. Our results suggest that EI is clinically useful and influenced by fat content, yet correction factors must account for more than SAT thickness alone and require further investigation.

背景 建立可互换的基于生物医学成像的临床评估方法来评估肌肉骨质疏松症，可能有助于预防肌肉萎缩，但目前既没有达成共识的方法，也不存在不同方法之间的转换。超声回波强度（EI）可评估肌骨软化症，但已证明皮下脂肪组织（SAT）厚度和使用者施力会影响 EI。尽管存在根据 SAT 厚度调整 EI 的校正因子，但它们都是根据较差的或没有参考测量值的情况建模的。根据可靠的肌骨质疏松症参考指标（如基于磁共振成像（MRI）的质子密度脂肪分数（PDFF））来建立 EI 修正模型，对于 EI 的临床应用非常必要。 方法 对健康的年轻人、健康的老年人和正在接受肺癌治疗的老年人（每组 10 人，女性占 50%）的右股直肌（RF）进行 0、5、10 和 15 N 的质子密度脂肪分数（PDFF）和 EI 测量。我们比较了不同力量和组间的 EI、SAT 厚度和 RF 厚度，并评估了经四种不同校正因子调整的 EI 与 PDFF 之间的关系。 结果 样本的平均年龄为 48.63 ± 19.68 岁，体重指数为 25.21 ± 5.19 kg/m2。PDFF 与原始 EI 之间的相关性为 r = 0.59（P < 0.001），与之前公布的校正因子（Young：0.62，P < 0.001；Neto Müller：0.61，P < 0.001）的相关性几乎可以忽略不计。不同力量之间的 EI、SAT 厚度和 RF 厚度差异不大（分别为 χ2 = 0.31，P = 0.957；χ2 = 2.39，P = 0.496；χ2 = 7.75，P = 0.051）。与老年人组相比，年轻健康成人的 EI 和 PDFF 明显较低（分别为 χ2 = 12.88，P = 0.002 和 χ2 = 9.13，P = 0.010）。 结论 无论力量大小，EI 都与 PDFF 相关，与之前公布的校正因子相比没有改进。我们的结果表明，EI 在临床上是有用的，并受脂肪含量的影响，但校正因子必须比 SAT 厚度单独考虑更多因素，因此需要进一步研究。
{"title":"Uncorrected and subcutaneous fat-corrected echo intensities are similarly associated with magnetic resonance imaging per cent fat","authors":"Benjamin Rush,&nbsp;Sujay Garlapati,&nbsp;Jevin Lortie,&nbsp;Katie Osterbauer,&nbsp;Timothy J. Colgan,&nbsp;Daiki Tamada,&nbsp;Toby C. Campbell,&nbsp;Anne Traynor,&nbsp;Ticiana Leal,&nbsp;Kenneth Lee,&nbsp;Scott B. Reeder,&nbsp;Adam J. Kuchnia","doi":"10.1002/rco2.92","DOIUrl":"https://doi.org/10.1002/rco2.92","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Establishing interchangeable biomedical imaging-based measures to assess myosteatosis clinically may lead to the prevention of muscle wasting, yet neither a consensus measure nor a conversion between measures exists. Ultrasound echo intensity (EI) potentially assesses myosteatosis, but subcutaneous adipose tissue (SAT) thickness and user force application have been shown to influence EI. Although correction factors exist to adjust EI for SAT thickness, they are modelled against poor or no reference measures. Modelling EI corrections against a robust reference measure of myosteatosis, like magnetic resonance imaging (MRI)-based proton density fat fraction (PDFF), is necessary for EI's clinical application.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Healthy young adults, healthy older adults, and older adults undergoing treatment for lung cancer (<i>n</i> = 10 per group with 50% females) had PDFF and EI at 0, 5, 10, and 15 N measured on their right rectus femoris (RF). We compared EI, SAT thickness, and RF thickness between forces and groups and assessed the relationships between EI adjusted by four different correction factors and PDFF.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>The mean age of our sample was 48.63 ± 19.68 years and had a body mass index of 25.21 ± 5.19 kg/m<sup>2</sup>. The correlation between PDFF and raw EI was <i>r</i> = 0.59 (<i>P</i> &lt; 0.001) with negligible increases by previously published correction factors (Young: 0.62, <i>P</i> &lt; 0.001; Neto Müller: 0.61, <i>P</i> &lt; 0.001). EI, SAT thickness, and RF thickness did not significantly differ between forces (<i>χ</i><sup>2</sup> = 0.31, <i>P</i> = 0.957; <i>χ</i><sup>2</sup> = 2.39, <i>P</i> = 0.496; and <i>χ</i><sup>2</sup> = 7.75, <i>P</i> = 0.051, respectively). EI and PDFF were significantly lower among young healthy adults compared with older adult groups (<i>χ</i><sup>2</sup> = 12.88, <i>P</i> = 0.002, and <i>χ</i><sup>2</sup> = 9.13, <i>P</i> = 0.010, respectively).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>EI is correlated with PDFF regardless of force with no improvement from previously published correction factors. Our results suggest that EI is clinically useful and influenced by fat content, yet correction factors must account for more than SAT thickness alone and require further investigation.</p>\u0000 </section>\u0000 </div>","PeriodicalId":73544,"journal":{"name":"JCSM rapid communications","volume":"7 1","pages":"66-75"},"PeriodicalIF":0.0,"publicationDate":"2024-05-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/rco2.92","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141475098","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
A genome wide association study to identify germline copy number variants associated with cancer cachexia: a preliminary analysis 通过基因组全关联研究确定与癌症恶病质相关的种系拷贝数变异：初步分析
JCSM rapid communications
Pub Date : 2024-04-18 DOI: 10.1002/rco2.91
Ashok Narasimhan, Mahalakshmi Kumaran, Ioannis Gioulbasanis, Richard J.E. Skipworth, Oliver F. Bathe, Stein Kaasa, Florian Strasser, Bruno Gagnon, Vickie Baracos, Sambasivarao Damaraju

Background

Cancer cachexia is characterized by severe loss of muscle and fat involving a complex interplay of host–tumour interactions. While much emphasis has been placed on understanding the molecular mechanisms associated with cachexia, understanding the heritable component of cachexia remains less explored. The current study aims to identify copy number variants (CNV) as genetic susceptibility determinants for weight loss in patients with cancer cachexia using genome wide association study (GWAS) approach.

Methods

A total of 174 age-matched patients with oesophagogastric or lung cancer were classified as weight losing (>10% weight loss) or weight stable participants (<2% weight loss). DNA was genotyped using Affymetrix SNP 6.0 arrays to profile CNVs. We tested CNVs with >5% frequency in the population for association with weight loss. Pathway analysis was performed using the genes embedded within CNVs. To understand if the CNVs in the present study are also expressed in skeletal muscle of patients with cachexia, we utilized two publicly available human gene expression datasets to infer the relevance of identified genes in the context of cachexia.

Results

Among the associated CNVs, 5414 CNVs had embedded protein coding genes. Of these, 1583 CNVs were present at >5% frequency. We combined multiple contiguous CNVs within the same genomic region and called them Copy Number Variable Region (CNVR). This led to identifying 896 non-redundant CNV/CNVRs, which encompassed 803 protein coding genes. Genes embedded within CNVs were enriched for several pathways implicated in cachexia and muscle wasting including JAK–STAT signalling, Oncostatin M signalling, Wnt signalling and PI3K-Akt signalling. This is the first proof of principle GWAS study to identify CNVs as genetic determinants for cancer cachexia. Further, we show that a subset of CNV/CNVR embedded genes identified in the current study are common with the previously published skeletal muscle gene expression datasets, indicating that expression of CNV/CNVR genes in muscle may have functional consequences in patients with cachexia. These genes include CPT1B, SPON1, LOXL1, NFAT5, RBFOX1, and PCSK6 to name a few.

Conclusions

This is the first proof of principle GWAS study to identify CNVs as genetic determinants for cancer cachexia. The data generated will aid in future replication studies in larger cohorts to account for genetic susceptibility to weig

背景癌症恶病质的特点是肌肉和脂肪严重流失，其中涉及宿主与肿瘤之间复杂的相互作用。尽管人们非常重视了解与恶病质相关的分子机制，但对恶病质遗传因素的了解仍然较少。本研究旨在利用全基因组关联研究（GWAS）方法确定拷贝数变异（CNV）作为癌症恶病质患者体重减轻的遗传易感性决定因素。 方法 共有 174 名年龄匹配的食管胃癌或肺癌患者被分为体重减轻者（体重减轻 10%）和体重稳定者（体重减轻 2%）。使用 Affymetrix SNP 6.0 阵列对 DNA 进行基因分型，以确定 CNV。我们测试了人群中频率为 5%的 CNV 与体重减轻的关系。利用嵌入 CNV 的基因进行了通路分析。为了了解本研究中的 CNV 是否也在恶病质患者的骨骼肌中表达，我们利用两个公开的人类基因表达数据集来推断所发现的基因与恶病质的相关性。 结果 在相关的 CNV 中，有 5414 个 CNV 嵌入了蛋白质编码基因。其中，1583 个 CNV 的出现频率为 5%。我们将同一基因组区域内多个连续的 CNVs 合并，称其为拷贝数可变区（CNVR）。这样就确定了 896 个非冗余 CNV/CNVR，其中包括 803 个蛋白质编码基因。嵌入 CNVs 的基因富集于与恶病质和肌肉萎缩有关的几个通路，包括 JAK-STAT 信号、Oncostatin M 信号、Wnt 信号和 PI3K-Akt 信号。这是首个将 CNVs 鉴定为癌症恶病质遗传决定因素的 GWAS 原理验证研究。此外，我们还发现，本研究中发现的一部分 CNV/CNVR 嵌入基因与之前发表的骨骼肌基因表达数据集具有共通性，这表明 CNV/CNVR 基因在肌肉中的表达可能会对恶病质患者产生功能性影响。这些基因包括 CPT1B、SPON1、LOXL1、NFAT5、RBFOX1 和 PCSK6 等。 结论 这是首次将 CNVs 确定为癌症恶病质遗传决定因素的原理性 GWAS 研究。所产生的数据将有助于今后在更大的队列中进行重复研究，以解释癌症恶病质患者体重减轻的遗传易感性。
{"title":"A genome wide association study to identify germline copy number variants associated with cancer cachexia: a preliminary analysis","authors":"Ashok Narasimhan,&nbsp;Mahalakshmi Kumaran,&nbsp;Ioannis Gioulbasanis,&nbsp;Richard J.E. Skipworth,&nbsp;Oliver F. Bathe,&nbsp;Stein Kaasa,&nbsp;Florian Strasser,&nbsp;Bruno Gagnon,&nbsp;Vickie Baracos,&nbsp;Sambasivarao Damaraju","doi":"10.1002/rco2.91","DOIUrl":"https://doi.org/10.1002/rco2.91","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Cancer cachexia is characterized by severe loss of muscle and fat involving a complex interplay of host–tumour interactions. While much emphasis has been placed on understanding the molecular mechanisms associated with cachexia, understanding the heritable component of cachexia remains less explored. The current study aims to identify copy number variants (CNV) as genetic susceptibility determinants for weight loss in patients with cancer cachexia using genome wide association study (GWAS) approach.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>A total of 174 age-matched patients with oesophagogastric or lung cancer were classified as weight losing (&gt;10% weight loss) or weight stable participants (&lt;2% weight loss). DNA was genotyped using Affymetrix SNP 6.0 arrays to profile CNVs. We tested CNVs with &gt;5% frequency in the population for association with weight loss. Pathway analysis was performed using the genes embedded within CNVs. To understand if the CNVs in the present study are also expressed in skeletal muscle of patients with cachexia, we utilized two publicly available human gene expression datasets to infer the relevance of identified genes in the context of cachexia.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Among the associated CNVs, 5414 CNVs had embedded protein coding genes. Of these, 1583 CNVs were present at &gt;5% frequency. We combined multiple contiguous CNVs within the same genomic region and called them Copy Number Variable Region (CNVR). This led to identifying 896 non-redundant CNV/CNVRs, which encompassed 803 protein coding genes. Genes embedded within CNVs were enriched for several pathways implicated in cachexia and muscle wasting including JAK–STAT signalling, Oncostatin M signalling, Wnt signalling and PI3K-Akt signalling. This is the first proof of principle GWAS study to identify CNVs as genetic determinants for cancer cachexia. Further, we show that a subset of CNV/CNVR embedded genes identified in the current study are common with the previously published skeletal muscle gene expression datasets, indicating that expression of CNV/CNVR genes in muscle may have functional consequences in patients with cachexia. These genes include CPT1B, SPON1, LOXL1, NFAT5, RBFOX1, and PCSK6 to name a few.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>This is the first proof of principle GWAS study to identify CNVs as genetic determinants for cancer cachexia. The data generated will aid in future replication studies in larger cohorts to account for genetic susceptibility to weig","PeriodicalId":73544,"journal":{"name":"JCSM rapid communications","volume":"7 1","pages":"55-65"},"PeriodicalIF":0.0,"publicationDate":"2024-04-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/rco2.91","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141475100","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Combined orchiectomy and limb immobilization recapitulate early age-related changes to skeletal muscle in mice 睾丸切除术和肢体固定相结合再现了小鼠骨骼肌早期与年龄有关的变化
JCSM rapid communications
Pub Date : 2024-04-16 DOI: 10.1002/rco2.90
Danielle A. Debruin, Jasmaine Murphy, Dean G. Campelj, Ryan Bagaric, Cara A. Timpani, Craig A. Goodman, Erik D. Hanson, Emma Rybalka, Alan Hayes

Background

Muscle mass and function decline in middle age, ultimately resulting in sarcopenia in the elderly and poor health outcomes, reducing quality of life. There is a lack of cost- and time-effective murine models that recapitulate the physiological changes associated with muscle mass decline to study possible interventions to delay sarcopenia. We aimed to evaluate the effectiveness of combining orchiectomy (ORC) surgery to simulate age-related androgen decline and hindlimb immobilization (IM) in inducing age-related skeletal muscle changes.

Methods

Four-month-old male C57BL/6J mice (n = 10) were subjected to ORC, followed by IM (right hindlimb casting) for 14 days. Upon completion of the casting period, ex vivo muscle contractile function, histology, and various mitochondrial markers were assessed, and results were compared with age-matched controls (CON; n = 8) and middle-aged (MA; 12 ± 1 months, n = 9) animals.

Results

IM combined with ORC induced a 30%–40% decrease in muscle mass across multiple hindlimb muscles (P < 0.0001), with the magnitude of muscle loss comparable with the MA group when corrected for body weight (P < 0.0001). In the IM limb of ORC mice, soleus muscle force significantly decreased when compared with the contralateral limb (P < 0.05) and aged-matched CON group (P < 0.05). The decrements in muscle force and mass present in the IM limb of ORC mice were accompanied by a 70% reduction in the expression of the muscle structural protein dystrophin and various mitochondrial markers, including cytochrome C (−55%), peroxisome proliferator-activated receptor gamma co-activator 1-beta (PGC1-β) (−49%), and cytochrome oxidase IV (COX-IV) (−73%) when compared with CON animals (P < 0.001). Lastly, our model also demonstrated specific fibre-type shifts in fast- and slow-twitch muscles, which mimicked changes in the MA group.

Conclusions

Applying treatments during IM could target acute muscle atrophy in MA adults, while applying them following cast removal in a low-testosterone environment could represent a window for rehabilitation therapeutics.

背景 肌肉质量和功能在中年时会下降，最终导致老年人肌肉疏松症和不良的健康状况，降低生活质量。目前缺乏成本低、时间短、效果好的小鼠模型来再现肌肉质量下降的相关生理变化，从而研究延缓肌肉疏松症的可能干预措施。我们旨在评估睾丸切除手术（ORC）模拟与年龄相关的雄激素下降和后肢固定（IM）在诱导与年龄相关的骨骼肌变化方面的有效性。 方法 对四个月大的雄性 C57BL/6J 小鼠（n = 10）进行睾丸切除手术，然后进行为期 14 天的右后肢固定。铸造期结束后，评估体内外肌肉收缩功能、组织学和各种线粒体标记物，并将结果与年龄匹配的对照组（CON；n = 8）和中年组（MA；12 ± 1 个月，n = 9）动物进行比较。 结果 IM 与 ORC 联用会导致后肢多块肌肉的肌肉质量下降 30%-40%（P < 0.0001），根据体重校正后，肌肉损失的程度与 MA 组相当（P < 0.0001）。与对侧肢体（P <0.05）和年龄匹配的CON组（P <0.05）相比，ORC小鼠IM肢体的比目鱼肌力显著下降。与对照组相比，ORC 小鼠肢体肌力和肌肉质量下降的同时，肌肉结构蛋白肌营养不良蛋白和各种线粒体标记物的表达也减少了 70%，其中包括细胞色素 C（-55%）、过氧化物酶体增殖激活受体伽马共激活因子 1-β（PGC1-β）（-49%）和细胞色素氧化酶 IV（COX-IV）（-73%）（P < 0.001）。最后，我们的模型还显示了快慢肌特定纤维类型的变化，这与 MA 组的变化相似。 结论 在 IM 期间应用治疗方法可针对 MA 成年人的急性肌肉萎缩，而在低睾酮环境中拆除石膏后应用治疗方法可代表康复疗法的一个窗口。
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引用次数: 0
Betulinic acid ameliorates cast-immobilized skeletal muscle atrophy but not denervation-induced skeletal muscle atrophy 白桦脂酸可改善石膏固定的骨骼肌萎缩，但不能改善去神经诱导的骨骼肌萎缩
JCSM rapid communications
Pub Date : 2024-04-01 DOI: 10.1002/rco2.89
Yuki Enoki, Yuki Kanezaki, Isamu Takahata, Kazuaki Taguchi, Kazuaki Matsumoto

Background

Terpenoids have gained attention as therapeutic agents for skeletal muscle atrophy owing to their various physiological activities. In this study, we screened four terpenoids for their therapeutic potential against muscle atrophy in cultured cells and evaluated the effectiveness of betulinic acid in two disuse muscle atrophy models.

Methods

C2C12 cells were used as the skeletal muscle model in cell culture experiments. Betulinic acid (100 mg/kg, twice daily) was administered to two different mouse models of muscle atrophy (established using the sciatic denervation and casting methods) for 7 days.

Results

In myotube experiments, the mRNA expression of atrogin-1 and myostatin was significantly suppressed by betulinic and ursolic acids (P < 0.05). In the differentiation phase of C2C12 myotubes, the mRNA expression levels of myoD and myogenin were significantly increased by betulinic acid (P < 0.05). In addition, apelin and irisin were also significantly increased by betulinic acid (P < 0.05 and 0.01, respectively). Consequently, betulinic acid was administered to the aforementioned muscle atrophy models. Betulinic acid did not inhibit the decrease in skeletal muscle weight observed in the denervation model. However, it significantly inhibited the decrease in tibialis anterior (TA) and extensor digitorum longus (EDL) weights and grip strength observed in the cast-immobilized skeletal muscle atrophy model (TA: Cast + Veh vs. Cast + Bet = 42.6 ± 1.0 vs. 46.0 ± 0.8 mg, P < 0.01; EDL: Cast + Veh vs. Cast + Bet = 9.0 ± 0.4 vs. 11.3 ± 0.5 mg, P < 0.01; grip strength: Cast + Veh vs. Cast + Bet = 222 ± 4.8 vs. 245 ± 3.6 g, P < 0.05). In addition, betulinic acid administration partially inhibited the decrease in skeletal muscle cross-sectional area.

Conclusions

Betulinic acid alleviated muscle atrophy in the cast model of muscle atrophy and has therapeutic potential for the treatment of immobilized disuse skeletal muscle atrophy.

背景 萜类化合物具有多种生理活性，因此作为骨骼肌萎缩的治疗药物已受到关注。本研究筛选了四种萜类化合物在培养细胞中对肌肉萎缩的治疗潜力，并评估了白桦脂酸在两种废用性肌肉萎缩模型中的有效性。 方法 在细胞培养实验中使用 C2C12 细胞作为骨骼肌模型。给两种不同的肌肉萎缩小鼠模型（使用坐骨神经去神经和铸造法建立）注射白桦脂酸（100 毫克/千克，每天两次），为期 7 天。 结果 在肌管实验中，白桦脂酸和熊果酸显著抑制了atrogin-1和myostatin的mRNA表达（P< 0.05）。在 C2C12 肌管的分化阶段，桦木酸可明显提高 myoD 和 myogenin 的 mRNA 表达水平（P < 0.05）。此外，凋亡素和鸢尾素也在白桦脂酸的作用下明显增加（P分别为0.05和0.01）。因此，将白桦脂酸用于上述肌肉萎缩模型。白桦脂酸不能抑制去神经模型中观察到的骨骼肌重量的减少。然而，白桦脂酸却能明显抑制在石膏固定骨骼肌萎缩模型中观察到的胫骨前肌（TA）和趾长伸肌（EDL）重量和握力的下降（TA：Cast + Veh vs. EDL：Cast + Bet = 42.6 ± 2.5 ± 2.5）。铸塑 + Bet = 42.6 ± 1.0 vs. 46.0 ± 0.8 mg，P < 0.01；EDL：铸塑 + Veh vs. 铸塑 + Bet = 9.0 ± 0.4 vs. 11.3 ± 0.5 mg，P < 0.01；握力：铸塑 + Veh vs. 铸塑 + Bet = 9.0 ± 0.4 vs. 11.3 ± 0.5 mg，P < 0.01）：Cast + Veh vs. Cast + Bet = 222 ± 4.8 vs. 245 ± 3.6 g，P < 0.05）。此外，白桦脂酸还能部分抑制骨骼肌横截面积的减少。 结论 白桦脂酸可缓解石膏模型肌肉萎缩，具有治疗固定失用性骨骼肌萎缩的潜力。
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