Yeo Jin Shin, Jae Won Yang, Heeyeon Jeong, Joyeong Kim, Bora Lee, Ji-Won Kim, Seung-Min Lee, Ju Yeon Kwak, Young Hoon Son, Kap Jung Kim, Yong Ryoul Yang, Chuna Kim, Ki-Sun Kwon, Kwang-Pyo Lee
{"title":"ExermiR-129-3p Enhances Muscle Function by Improving Mitochondrial Activity Through PARP1 Inhibition","authors":"Yeo Jin Shin, Jae Won Yang, Heeyeon Jeong, Joyeong Kim, Bora Lee, Ji-Won Kim, Seung-Min Lee, Ju Yeon Kwak, Young Hoon Son, Kap Jung Kim, Yong Ryoul Yang, Chuna Kim, Ki-Sun Kwon, Kwang-Pyo Lee","doi":"10.1002/jcsm.13823","DOIUrl":"https://doi.org/10.1002/jcsm.13823","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Physical exercise has beneficial effects on various organs, including skeletal muscle. However, not all patients are capable of engaging in exercise to maintain muscle function, which underscores the importance of identifying molecular mechanisms of physical training that could lead to the discovery of exercise-mimicking molecules.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>This study sought to identify molecular mediators of exercise that could improve muscle function. We focused on the exercise-induced microRNA (miR)-129-3p, investigating its role and effects on mitochondrial activity both in vivo and in vitro. The expression of miR-129-3p was analysed in skeletal muscle following exercise, and its downstream effects on the poly (ADP-ribose) polymerase-1 (Parp1)-SIRT1-PGC1α signalling pathway were elucidated. Functional studies were conducted using muscle-specific overexpression of miR-129-3p in adult mice and intramuscular injection of AAV9-miR-129-3p in obese mice to assess exercise capacity and muscle strength.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Exercise was found to upregulate miR-129-3p in skeletal muscle (<i>p</i> < 0.05), which directly inhibits <i>Parp1</i>, a major NAD<sup>+</sup>-consuming enzyme. This inhibition leads to increased NAD<sup>+</sup> levels (<i>p</i> < 0.05), activating SIRT1 and subsequently reducing the acetylation of PGC1α, thereby enhancing mitochondrial function. Muscle-specific overexpression of miR-129-3p in adult mice significantly enhanced exercise capacity (> 130%, <i>p</i> < 0.0001), while AAV9-miR-129-3p injections ameliorated muscle weakness (twitch force, > 140%, <i>p</i> < 0.05; tetanic force, > 160%, <i>p</i> < 0.01) in obese mice. In human skeletal muscle myoblasts, miR-129-3p improved mitochondrial function via the PARP1-SIRT1-PGC1α signalling pathway.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>Our findings suggest that miR-129-3p, induced by exercise, can mimic the beneficial effects of physical exercise. This highlights miR-129-3p as a potential therapeutic target for improving muscle health, especially in individuals unable to exercise.</p>\u0000 </section>\u0000 </div>","PeriodicalId":48911,"journal":{"name":"Journal of Cachexia Sarcopenia and Muscle","volume":"16 2","pages":""},"PeriodicalIF":9.4,"publicationDate":"2025-04-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jcsm.13823","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143852912","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Estimated Glucose Disposal Rate Associated With Risk of Frailty and Likelihood of Reversion","authors":"Dingchun Hou, Shangjun Liu, Yumei Sun, Chang Liu, Xue Shang, Lijun Pei, Gong Chen","doi":"10.1002/jcsm.13814","DOIUrl":"https://doi.org/10.1002/jcsm.13814","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Estimated glucose disposal rate (eGDR) is a simple and effective measure for insulin resistance, which is associated with higher risk of frailty. We aim to analyse the associations of eGDR with frailty risk and its reversibility.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>A population-based longitudinal study was conducted of 11 670 participants from the China Health and Retirement Longitudinal Study and 19 355 participants from the Health and Retirement Study. Frailty was assessed by the frailty index and reversibility was measured by transitions from frailty at baseline to non-frailty during follow-up. The eGDR was divided into Q<sub>1</sub>, Q<sub>2</sub>, Q<sub>3</sub> and Q<sub>4</sub> according to the quartiles. Multi-state Markov model was performed to evaluate the effects of eGDR on transitions among non-frailty, frailty and death. Cox regression model was used to estimate eGDR associated with the risk of frailty and the likelihood of reversion.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>In Chinese population characterized by a median age of 60 years (IQR: 54–66) with 6119 women (52.43%), compared with the Q<sub>1</sub> level of eGDR, participants exposure to Q<sub>3</sub> and Q<sub>4</sub> level decreased the probability of transitioning from non-frailty to frailty by 22% (HR = 0.78, 95% CI: 0.69–0.88) and 25% (HR = 0.75, 95% CI: 0.66–0.86), respectively. But its Q<sub>2</sub>, Q<sub>3</sub> and Q<sub>4</sub> levels increased the probability of transitioning from frailty to non-frailty by 24% (HR = 1.24, 95% CI: 1.06–1.44), 39% (HR = 1.39, 95% CI: 1.19–1.64) and 33% (HR = 1.33, 95% CI: 1.13–1.58). In American population with a median age of 63 years (IQR: 56–72) and 11 189 women (57.81%), its Q<sub>2</sub>, Q<sub>3</sub> and Q<sub>4</sub> levels decreased the probability of transitioning from non-frailty to frailty by 17% (HR = 0.83, 95% CI: 0.77–0.89), 24% (HR = 0.76, 95% CI: 0.70–0.82) and 46% (HR = 0.54, 95% CI: 0.49–0.59), respectively. The probability of revising frailty increased by 25% (HR = 1.25, 95% CI: 1.13–1.38), 36% (HR = 1.36, 95% CI: 1.22–1.51) and 48% (HR = 1.48, 95% CI: 1.30–1.69) for levels Q<sub>2</sub>, Q<sub>3</sub> and Q<sub>4</sub>. As shown in the prospective analysis, increased eGDR levels from Q<sub>2</sub> to Q<sub>4</sub> were associated with decreased frailty risk and higher likelihood of reversion, as evidenced by the dose–response relationship revealed by restricted cubic spline analysis.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>Higher levels of eGDR were ","PeriodicalId":48911,"journal":{"name":"Journal of Cachexia Sarcopenia and Muscle","volume":"16 2","pages":""},"PeriodicalIF":9.4,"publicationDate":"2025-04-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jcsm.13814","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143846175","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}
Hamzah Amin, Michelle G. Swainson, Muhammed Aqib Khan, Marwan Bukhari
{"title":"Association of a Combined Body Mass Index and Regional Body Fat Percentage Metric With Fragility Fracture Risk: Evidence from a Large Observational Cohort","authors":"Hamzah Amin, Michelle G. Swainson, Muhammed Aqib Khan, Marwan Bukhari","doi":"10.1002/jcsm.13808","DOIUrl":"https://doi.org/10.1002/jcsm.13808","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Evidence suggests that high body fat and low muscle mass may increase the risk of fragility fractures. However, current fracture risk models, which largely rely on body mass index (BMI), may not fully capture these compositional factors. We recommend integrating additional body composition variables into fracture risk calculators to improve accuracy. Previously, we described partial body fat percentage (PBF%), a novel measure that is routinely available and calculated as the proportion of fat at the lumbar spine and hip during DXA scans. We hypothesize that a combined BMI and PBF% approach (BMI/PBF%) could be associated with fragility fracture.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Patients were referred to our DXA scanner between June 2004 and February 2024 and had combined lumbar spine and bilateral femoral scans. Patients were initially categorized by BMI (underweight, normal weight, overweight and obese) and then divided into tertiles of PBF%. Based on each patient's unique combination of BMI and PBF% tertile, they were stratified into 12 binary BMI/PBF% groups for analysis. Multivariable logistic regression models, reporting odds ratios (OR), with BMI/PBF% groups as the independent variables and fragility fractures as the dependent variable were fit, with all results adjusted for known fracture risk factors.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>We analysed 36 235 patients (83.4% female, 16.6% male), of whom 14 342 (39.5%) reported fragility fractures. The median (IQR) age was 67.7 (57.5–75.0) years, with a BMI of 26.4 (23.3–30.2) kg/m<sup>2</sup> and PBF% of 30.6% (25.5% – 35.4%). In females, those in the lowest PBF% tertile had reduced odds of fragility fractures across all BMI categories (e.g., obese low PBF%: OR 0.70, 95% CI 0.64–0.78), whereas in males, this reduction was observed only amongst overweight and obese individuals (e.g., obese low PBF%: OR 0.71, 95% CI 0.57–0.88). No association was found for patients in the middle PBF% tertile across any BMI group. In contrast, females in the highest PBF% tertile exhibited increased odds of fractures across all BMI categories except underweight (e.g., obese high PBF%: OR 1.31, 95% CI 1.22–1.42), and a similar pattern was seen in males, but limited to the overweight and obese groups (e.g., obese high PBF%: OR 1.27, 95% CI 1.04–1.55).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>High or low PBF% within BMI categories is associated with fragility fractures, challenging the traditional notion that high BMI protects against fractures. Thi","PeriodicalId":48911,"journal":{"name":"Journal of Cachexia Sarcopenia and Muscle","volume":"16 2","pages":""},"PeriodicalIF":9.4,"publicationDate":"2025-04-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jcsm.13808","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143840811","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}
Xiao-xu Wang, Jing-yuan Cao, Yao Wang, Min Li, Shi-mei Hou, Zhen Zhao, Min Yang, Ping-ping Ju, Yu-jia Jiang, Jing-jie Xiao, Ri-ring Tang, Hong Liu, Bi-cheng Liu, Xiao-liang Zhang, Bin Wang
{"title":"Association of Muscle Radiodensity and Muscle Mass With Thoracic Aortic Calcification Progression in Dialysis Patients","authors":"Xiao-xu Wang, Jing-yuan Cao, Yao Wang, Min Li, Shi-mei Hou, Zhen Zhao, Min Yang, Ping-ping Ju, Yu-jia Jiang, Jing-jie Xiao, Ri-ring Tang, Hong Liu, Bi-cheng Liu, Xiao-liang Zhang, Bin Wang","doi":"10.1002/jcsm.13813","DOIUrl":"https://doi.org/10.1002/jcsm.13813","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Recent findings have spotlighted sarcopenia as a critical factor exacerbating cardiovascular risk in dialysis patients. However, no studies have investigated the relationship of muscle characteristics with thoracic aortic calcification (TAC). We explored whether skeletal muscle radiodensity (SMD) and skeletal muscle index (SMI) are associated with TAC in dialysis patients.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>In this study, 2517 dialysis patients (between January 2020 and June 2023) from four centres with chest computed tomography (CT) scans were analysed cross-sectionally. A cohort of 544 initial-dialysis patients (between January 2014 and December 2020) was followed for TAC progression. Chest CT images were used to assess SMD and SMI at the L1 level, as well as to measure the scores of TAC, including ascending TAC (ATAC), aortic arch calcification (AoAC) and descending TAC (DTAC). Multivariable linear regression models were employed to assess the effects of SMD and SMI on TAC and its progression. Restricted cubic spline was used to assess the potential non-linear relationships of SMD and SMI with TAC progression.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>The mean (SD) age for the cross-sectional study was 54.8 (14.0) years, with males accounting for 58.2%. Over a mean (SD) follow-up duration of 3.45 (1.82) years, 85.7% showed TAC progression. Comparing the highest quartile of SMD to the lowest quartile, a significant inverse association was observed with TAC (<i>β</i>, −1.08 [−1.42 to −0.75]; <i>p</i> < 0.001); similar trends were noted for SMI (<i>β</i>, −0.42 [−0.74 to −0.10]; <i>p</i> = 0.011). SMD and SMI as continuous variables were also both significantly negatively correlated with TAC. In the longitudinal study, multivariable linear regression models revealed that an increase of 1 SD in SMD resulted in a decrease of 0.10 SD (95% CI, −0.17 to −0.02; <i>p</i> = 0.011) in TAC progression, and an increase of 1 SD in SMI resulted in a decrease of 0.12 SD (95% CI, −0.20 to −0.04; <i>p</i> = 0.003) in TAC progression. Restricted cubic spline models excluded non-linear trends for the relationships of SMD and SMI with TAC progression. The associations of SMD and SMI with DTAC were consistent with those observed for TAC, but neither showed a significant association with ATAC.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>Higher SMD and higher SMI were significantly associated with lower TAC and its progression in dialysis patients. Improving SMD and SMI could be a new approach for reducing ","PeriodicalId":48911,"journal":{"name":"Journal of Cachexia Sarcopenia and Muscle","volume":"16 2","pages":""},"PeriodicalIF":9.4,"publicationDate":"2025-04-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jcsm.13813","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143840648","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Comment on “Risk of Sarcopenia Following Long-Term Statin Use in Community-Dwelling Middle-Aged and Older Adults in Japan” by Huang et al.","authors":"Jian Huang","doi":"10.1002/jcsm.13801","DOIUrl":"https://doi.org/10.1002/jcsm.13801","url":null,"abstract":"<p>I read with great interest the article ‘Risk of Sarcopenia Following Long-Term Statin Use in Community-Dwelling Middle-Aged and Older Adults in Japan’ by Huang et al. [<span>1</span>]. Although the study addresses a topic of significant clinical relevance, I would like to express concerns regarding two critical methodological aspects that may affect the internal validity of the findings.</p><p>First, the article reported that after propensity score matching, several variables, including age, exhibit a standardized mean difference (SMD) of exactly 0.00 (see Table 1). Such a perfect balance for a continuous variable is highly unlikely, even with state-of-the-art matching techniques, and strongly suggests a potential data or calculation error. Previous research has consistently demonstrated that, in practice, residual imbalances almost invariably persist despite careful matching [<span>2</span>]. Greater transparency in reporting balance diagnostics, for example, by providing graphical representations of propensity score distributions such as Love plots or density plots, would allow readers to thoroughly assess the adequacy of the matching process and verify that the matching has achieved an acceptable balance between groups.</p><p>Second, the authors employed risk set sampling to construct the control group; however, the article did not provide sufficient details regarding the specific algorithm used or its potential limitations. Risk set sampling is a critical method for addressing time-dependent confounding in longitudinal studies [<span>3</span>], yet its implementation can vary considerably and may introduce biases if not carefully executed. The study did not specify how subjects were selected, the exact matching procedures used when sampling with replacement or any assumptions underlying the method. A detailed description of the risk set sampling algorithm, along with a discussion of its limitations and any potential impact on the study's conclusions, is essential for evaluating the robustness and reproducibility of the analysis.</p><p>These points warrant further clarification, as they have significant implications for the interpretation of the study's results.</p><p>The author declares no conflicts of interest.</p>","PeriodicalId":48911,"journal":{"name":"Journal of Cachexia Sarcopenia and Muscle","volume":"16 2","pages":""},"PeriodicalIF":9.4,"publicationDate":"2025-04-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jcsm.13801","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143840649","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}
Mingchong Liu, Jiaming Wang, Chensong Yang, Guixin Sun
{"title":"Estimation of Appendicular Skeletal Muscle Mass in Studies Based on CHARLS May Cause Unreliable Conclusion","authors":"Mingchong Liu, Jiaming Wang, Chensong Yang, Guixin Sun","doi":"10.1002/jcsm.13800","DOIUrl":"https://doi.org/10.1002/jcsm.13800","url":null,"abstract":"<p>We write to highlight a potential issue in the estimation of appendicular skeletal muscle mass (ASM) in studies based on the China Health and Retirement Longitudinal Study (CHARLS). In recent years, numerous studies based on the CHARLS database have been published, with a significant number focusing on sarcopenia. A PubMed search reveals that over 94 sarcopenia-related articles based on CHARLS data have been published to date, with the majority appearing in the past 3 years. Our journal has also contributed to this body of literature by publishing several of these studies [<span>1, 2</span>]. Although these studies have contributed significantly to the field, we argue that the estimation of ASM in many of these studies may be based on unreliable methods, potentially leading to questionable conclusions.</p><p>The accurate estimation of ASM is crucial for the diagnosis of sarcopenia and the assessment of its prevalence and impact. Although this formula has been widely used, we contend that its application in CHARLS-based studies may be inappropriate for several reasons.</p><p>First, the original study from which this formula was derived was conducted in a relatively young population with a mean age of only about 40 years (39.3 ± 14.5 years for males; 41.1 ± 14.1 years for females; 18–69 years old). In contrast, sarcopenia research primarily focuses on older adults, and the physiological characteristics of muscle mass in younger individuals may not be representative of those in the elderly. The sarcopenia research based on CHARLS usually excludes individuals younger than 60, with a mean age of more than 67 [<span>1, 2</span>]. This age discrepancy can significantly impact the applicability and accuracy of the derived formula in sarcopenia research.</p><p>Second, the original study was conducted in 2006, whereas many CHARLS data used in recent studies were collected around 2015 [<span>1</span>]. According to data from the General Administration of Sport of China (https://www.sport.gov.cn/n315/index.html), significant changes in the average height and weight of the Chinese population have occurred over the past two decades. These changes may affect the accuracy of ASM estimation using the original formula.</p><p>Another critical limitation of the widely used formula is its reliance on only a few anthropometric measurements—height, weight, sex and age—while neglecting other important body composition indicators such as waist circumference and calf circumference. This oversimplification can lead to substantial bias in the estimation of ASM. For example, using a fixed cut-off point based on the lowest 20th percentile of ASM, as seen in many CHARLS-based studies [<span>1, 2</span>], may incorrectly classify individuals with low stature and average weight as having low ASM. This approach essentially labels a fixed proportion of the population as having low muscle mass, regardless of their actual muscle status. The exclusion of other relevant anthropomet","PeriodicalId":48911,"journal":{"name":"Journal of Cachexia Sarcopenia and Muscle","volume":"16 2","pages":""},"PeriodicalIF":9.4,"publicationDate":"2025-04-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jcsm.13800","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143840798","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}
Tiril Tøien, Ole Kristian Berg, Roberto Modena, Mathias Forsberg Brobakken, Eivind Wang
{"title":"Heavy Strength Training in Older Adults: Implications for Health, Disease and Physical Performance","authors":"Tiril Tøien, Ole Kristian Berg, Roberto Modena, Mathias Forsberg Brobakken, Eivind Wang","doi":"10.1002/jcsm.13804","DOIUrl":"https://doi.org/10.1002/jcsm.13804","url":null,"abstract":"<p>Older adults typically exhibit reductions in skeletal muscle maximal strength and the ability to produce force rapidly. These reductions are often augmented by concomitant acute and chronic diseases, resulting in attenuated physical performance and higher propensity of falls and injuries. With the proportion of older adults in the population increasing, there is an alarming need for cost-effective strategies to improve physical performance and combat a multitude of age-related diseases. Surprisingly, despite convincing evidence emerging over three decades that strength training can substantially improve maximal strength (1RM), rate of force development (RFD) and power, contributing to improved health, physical performance and fall prevention, it appears that it has not fully arrived at the older adults' doorsteps. The aim of the current narrative review is to accentuate the convincing benefits of strength training in healthy and diseased older adults. As intensity appears to play a key role for improvements in 1RM, RFD and power, this review will emphasize training performed with heavy (80%–84% of 1RM) and very heavy loads (≥ 85% of 1RM), where the latter is often referred to as maximal strength training (MST). MST uses loads of ~90% of 1RM, which can only be performed a maximum of 3–5 times, 3–5 sets and maximal intentional concentric velocity. Strength training performed with loads in the heavy to very heavy domain of the spectrum may, because of the large increases in muscle strength, focuses on neural adaptations and relatively low risk, provides additional benefits for older adults and contrasts current guidelines which recommend low-to-moderate intensity (60%–70% of 1RM) and slow-moderate concentric velocity. This review also provides information on practical application of MST aimed at practitioners who are involved with preventive and/or rehabilitative health care for older adults.</p>","PeriodicalId":48911,"journal":{"name":"Journal of Cachexia Sarcopenia and Muscle","volume":"16 2","pages":""},"PeriodicalIF":9.4,"publicationDate":"2025-04-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jcsm.13804","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143840799","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Andrea Irazoki, Emma Frank, Tang Cam Phung Pham, Jessica L. Braun, Amy M. Ehrlich, Mark Haid, Fabien Riols, Camilla Hartmann Friis Hansen, Anne-Sofie Rydal Jørgensen, Nicoline Resen Andersen, Laura Hidalgo-Corbacho, Roberto Meneses-Valdes, Mona Sadek Ali, Steffen Henning Raun, Johanne Louise Modvig, Samantha Gallero, Steen Larsen, Zach Gerhart-Hines, Thomas Elbenhardt Jensen, Maria Rohm, Jonas T. Treebak, Val Andrew Fajardo, Lykke Sylow
{"title":"Housing Temperature Impacts the Systemic and Tissue-Specific Molecular Responses to Cancer in Mice","authors":"Andrea Irazoki, Emma Frank, Tang Cam Phung Pham, Jessica L. Braun, Amy M. Ehrlich, Mark Haid, Fabien Riols, Camilla Hartmann Friis Hansen, Anne-Sofie Rydal Jørgensen, Nicoline Resen Andersen, Laura Hidalgo-Corbacho, Roberto Meneses-Valdes, Mona Sadek Ali, Steffen Henning Raun, Johanne Louise Modvig, Samantha Gallero, Steen Larsen, Zach Gerhart-Hines, Thomas Elbenhardt Jensen, Maria Rohm, Jonas T. Treebak, Val Andrew Fajardo, Lykke Sylow","doi":"10.1002/jcsm.13781","DOIUrl":"https://doi.org/10.1002/jcsm.13781","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Cancer cachexia, affecting up to 80% of patients with cancer, is characterized by muscle and fat loss with functional decline. Preclinical research seeks to uncover the molecular mechanisms underlying cachexia to identify potential targets. Housing laboratory mice at ambient temperature induces cold stress, triggering thermogenic activity and metabolic adaptations. Yet, the impact of housing temperature on preclinical cachexia remains unknown.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Colon 26 carcinoma (C26)-bearing and PBS-inoculated (Ctrl) mice were housed at standard (ST; 20°C–22°C) or thermoneutral temperature (TN; 28°C–32°C). They were monitored for body weight, composition, food intake and systemic factors. Upon necropsy, tissues were weighed and used for evaluation of ex vivo force and respiration, or snap frozen for biochemical assays.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>C26 mice lost 7.5% body weight (<i>p</i> = 0.0001 vs. Ctrls), accounted by decreased fat mass (−35%, <i>p</i> < 0.0001 vs. Ctrls), showing mild cachexia irrespective of housing temperature. All C26 mice exhibited reduced force (−40%, <i>p</i> < 0.0001 vs. Ctrls) and increased atrogene expression (3-fold, <i>p</i> < 0.003 vs. Ctrls). Cancer altered white adipose tissue (WAT)'s functional gene signature (49%, <i>p</i> < 0.05 vs. Ctrls), whereas housing temperature reduced brown adipose tissue (BAT)'s (−78%, <i>p</i> < 0.05 vs. ST Ctrl). Thermogenic capacity measured by <i>Ucp1</i> expression decreased upon cancer in both WAT and BAT (−93% and −63%, <i>p</i> < 0.0044 vs. Ctrls). Cancer-driven glucose intolerance was noted at ST (26%, <i>p</i> = 0.0192 vs. ST Ctrl), but restored at TN (−23%, <i>p</i> = 0.005 vs. ST C26). Circulating FGF21, GDF-15 and IL-6 increased in all C26 mice (4-fold, <i>p</i> < 0.009 vs. Ctrls), with a greater effect on IL-6 at TN (76%, <i>p</i> = 0.0018 vs. ST C26). Tumour and WAT <i>Il6</i> mRNA levels remained unchanged, while cancer induced skeletal muscle (SkM) <i>Il6</i> (2-fold, <i>p</i> = 0.0016 vs. Ctrls) at both temperatures. BAT <i>Il6</i> was only induced in C26 mice at TN (116%, <i>p</i> = 0.0087 vs. ST C26). At the bioenergetics level, cancer increased SkM SERCA ATPase activity at ST (4-fold, <i>p</i> = 0.0108 vs. ST Ctrl) but not at TN. In BAT, O<sub>2</sub> consumption enhanced in C26 mice at ST (119%, <i>p</i> < 0.03 vs. ST Ctrl) but was blunted at TN (−44%, <i>p</i> < 0.0001 vs. ST C26). Cancer increased BAT ATP levels regardless of temperature (2-fold, <i>p</i> = 0.0046 vs. Ctrls), while SERCA ATPase activity remained unchanged at ST and decreased at TN (−","PeriodicalId":48911,"journal":{"name":"Journal of Cachexia Sarcopenia and Muscle","volume":"16 2","pages":""},"PeriodicalIF":9.4,"publicationDate":"2025-04-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jcsm.13781","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143835942","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Loss of popdc3 Impairs Mitochondrial Function and Causes Skeletal Muscle Atrophy and Reduced Swimming Ability in Zebrafish","authors":"Chen-Chen Sun, Zhang-Lin Chen, Dong Yang, Jiang-Ling Xiao, Xiang-Tao Chen, Xi-Yang Peng, Xiu-Shan Wu, Chang-Fa Tang","doi":"10.1002/jcsm.13794","DOIUrl":"https://doi.org/10.1002/jcsm.13794","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>The Popeye domain containing 3 (POPDC3) protein is essential for the maintenance of skeletal muscle homeostasis. POPDC3 is a pathogenic variant gene of limb-girdle muscular dystrophy (LGMD), and its variants lead to LGMDR26. At the animal level, zebrafish larvae with <i>popdc3</i> mutations develop tail curls and muscle atrophy. However, the mechanism of skeletal muscle atrophy induced by <i>POPDC3</i> variants/loss remains unclear.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Eight-month-old male WT and <i>popdc3</i> mKO zebrafish were used for this research. Loli Track (Denwmark) and Loligo Swimming Respirometer were used to observe the zebrafish's swimming ability. The zebrafish skeletal muscle structure and cross-sectional area (CSA) were observed and counted by transmission electron microscopy (TEM), H&E and wheat germ agglutinin (WGA). Enriched genes and signalling pathways were analysed using RNA sequencing, and the effects of <i>popdc3</i> mKO on zebrafish skeletal muscle mitochondrial respiration, biogenesis and dynamics were examined to investigate possible mechanisms.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>The swimming ability of <i>popdc3</i> mKO zebrafish was reduced, and as evidenced by the reluctance to move, fewer movement trajectories, the total distance travelled (<i>p</i> < 0.001), the average velocity of movement (<i>p</i> < 0.001), oxygen consumption (MO<sub>2</sub>) (<i>p</i> < 0.01), maximum oxygen consumption (MO<sub>2max</sub>) (<i>p</i> < 0.05), critical swimming speed (U<sub>crit</sub>) (<i>p</i> < 0.01) and relative swimming speed (U<sub>crit-r</sub>) (<i>p</i> < 0.01) were significantly decreased and increased of the exhaustive swimming time (<i>p</i> < 0.01). In addition, loss of <i>popdc3</i> reduced zebrafish skeletal muscle weight (<i>p</i> < 0.001), muscle/body weight (<i>p</i> < 0.01), myofibre size and CSA (<i>p</i> < 0.01), increased protein degradation (ubiquitination and autophagy) (<i>p</i> < 0.05) and decreased protein synthesis (<i>p</i> < 0.05), suggesting that <i>popdc3</i> deficiency induces zebrafish skeletal muscle atrophy. Further, <i>popdc3</i> mKO zebrafish mitochondrial function is reduced, as evidenced by impaired mitochondrial respiration, decreased biogenesis and kinetic imbalance (<i>p</i> < 0.05).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>POPDC3, a Popeye protein, plays an important role in controlling mitochondrial function and skeletal muscle mass and strength. Loss of <i>popdc3</i> decreases m","PeriodicalId":48911,"journal":{"name":"Journal of Cachexia Sarcopenia and Muscle","volume":"16 2","pages":""},"PeriodicalIF":9.4,"publicationDate":"2025-04-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jcsm.13794","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143835941","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Jin Hyun Kim, Seunghye Lee, Hani Jang, Sehyun Jung, Myeong Hee Jung, Jeong Won Yun, Haejin Jeon, Hyun-Jung Kim, Se-Ho Chang, Eun Ju Lee, Hyo-Soo Kim
{"title":"Transcriptional Intermediary Factor 1γ–Induced Irisin in Skeletal Muscle Attenuates Renal Fibrosis in Diabetic Nephropathy","authors":"Jin Hyun Kim, Seunghye Lee, Hani Jang, Sehyun Jung, Myeong Hee Jung, Jeong Won Yun, Haejin Jeon, Hyun-Jung Kim, Se-Ho Chang, Eun Ju Lee, Hyo-Soo Kim","doi":"10.1002/jcsm.13810","DOIUrl":"https://doi.org/10.1002/jcsm.13810","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Transcriptional intermediary factor 1γ (TIF1γ) is a negative regulator of TGF-β1 signalling and has been associated with patient survival in renal cell carcinoma. However, its role in diabetes mellitus (DM), particularly in diabetic nephropathy (DN), remains unclear. DN is the leading cause of chronic kidney disease (CKD). We investigated the potential role of TIF1γ in mitigating multiple DM-related complications.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Mice were divided into four groups: <i>db</i>/m+, <i>db/db</i> and <i>db/db</i> mice treated with cytomegalovirus- or TGF-TIF1γ plasmids (40 μg/mouse; intraperitoneally weekly for 16 weeks). Renal injury, fibrosis, function and gene expression related to fibrosis and epithelial–mesenchymal transition (EMT) in the kidneys were assessed. Muscle atrophy, regeneration markers, myokine levels and exercise capacity were evaluated. C2C12 cells were exposed to palmitate with or without TIF1γ transfection, and irisin expression and secretion were measured. Muscle-kidney crosstalk was analysed using conditioned media (CM) from TIF1γ-transfected C2C12 cells in palmitate-treated human kidney (HK)-2 cells. Additionally, HK-2 cells were incubated in CM from fibronectin type III domain-containing protein (FNDC)5-knockdown C2C12 cells to confirm irisin-mediated kidney crosstalk by TIF1γ.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>TIF1γ treatment in <i>db/db</i> mice resulted in a significant attenuation of renal tubulointerstitial fibrosis (1.5-fold decrease), glomerular injury (1.8-fold improvement), tubular injury (1.6-fold improvement), renal dysfunction (1.7-fold improvement) and a reduction in EMT-related factors (1.8-fold decrease) (<i>p</i> < 0.05). The levels of administered TIF1γ plasmids were higher in skeletal muscle than in renal tissues. TIF1γ expression was significantly elevated in the skeletal muscle of <i>db/db</i> mice treated with TIF1γ plasmids (6.5-fold) (<i>p</i> < 0.05). Mice receiving both plasmids exhibited a 1.8-fold reduction in pathological muscle morphology and atrophy-related gene expression, a 3.0-fold increase in regeneration-related gene expression and a 1.6-fold improvement in muscle function (<i>p</i> < 0.05). Irisin expression increased by 2.1-fold in skeletal muscle and serum (<i>p</i> < 0.05). In TIF1γ-transfected C2C12 cells, irisin secretion was elevated by 1.5-fold (<i>p</i> < 0.05). CM from TIF1γ-transfected C2C12 cells attenuated EMT in palmitate-treated HK-2 cells, compared with medium from nontransfected C2C12 cells (1.9-fold improvement [<i>p</i> < 0.05]). Conversely, FNDC5 knockdown in C2C12 cells accel","PeriodicalId":48911,"journal":{"name":"Journal of Cachexia Sarcopenia and Muscle","volume":"16 2","pages":""},"PeriodicalIF":9.4,"publicationDate":"2025-04-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jcsm.13810","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143835874","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}