Journal of Cachexia Sarcopenia and Muscle最新文献

Long-Term Effects of High-Intensity Aerobic Training on Metabolic Syndrome: An 8-Year Follow-Up Randomized Clinical Trial

IF 9.4 1区医学 Q1 GERIATRICS & GERONTOLOGY

Journal of Cachexia Sarcopenia and Muscle

Pub Date : 2025-04-02 DOI: 10.1002/jcsm.13780

Felix Morales-Palomo, Alfonso Moreno-Cabañas, Laura Alvarez-Jimenez, Diego Mora-Gonzalez, Ricardo Mora-Rodriguez

<div> <section> <h3> Background</h3> <p>Metabolic syndrome (MetS) is a set of five cardiometabolic risk factors that typically worsen with age. One exercise-training programme is effective at improving those factors in middle-aged individuals with MetS. To our knowledge, exercise-training efficacy as MetS individuals age has not been explored. This study determined the effectiveness of a periodized exercise training programme for individuals with MetS after a follow-up period of 8 years.</p> </section> <section> <h3> Methods</h3> <p>Forty-seven individuals with MetS were block-randomized into an EXERCISE (<i>n</i> = 22, 52 ± 8 years old, 23% women) or a CONTROL group (<i>n</i> = 25, 53 ± 8 years old, 32% women). Both groups received standard health care, including medical counselling and lifestyle advice at least every 6 months, while participants in EXERCISE also underwent a supervised exercise programme. The intervention lasted 8 years and consisted of 4 months per year (November to March) of high-intensity interval training thrice weekly. At baseline, and after 4 and 8 years of treatment, we assessed body composition, MetS components (i.e., MetS <i>Z</i> score), medication use, cardiorespiratory fitness (CRF; assessed by VO<sub>2MAX</sub>) and maximal leg cycling power output (W<sub>MAX</sub>).</p> </section> <section> <h3> Results</h3> <p>Paradoxically, MetS <i>Z</i> score and body weight were reduced after 8 years (subjects aged from 52 to 60 years old) in both groups (time effect <i>p</i> < 0.001 and <i>p</i> = 0.008; time × group interaction <i>p</i> = 0.253 and <i>p</i> = 0.130). However, in those 8 years, the medicine use score increased threefold in CONTROL (137% increase; from 1.7 to 3.9; <i>p</i> < 0.001) while it did not change in EXERCISE (33%; from 2.0 to 2.7; <i>p</i> = 0.066). In 8 years, CRF and W<sub>MAX</sub> increased in EXERCISE by 14% (3.4 ± 5.6 mL·kg<sup>−1</sup>·min<sup>−1</sup>) and 4% (7 ± 37 W) while decreasing in CONTROL by −7% (−1.6 ± 3.4 mL·kg<sup>−1</sup>·min<sup>−1</sup>) and −14% (−24 ± 27 W) being different between groups after 4 and 8 years (both time × group interaction <i>p</i> = 0.002). Pearson correlations showed that MetS <i>Z</i> score improvements were significantly associated with increases in medication use score in the CONTROL group (<i>r</i> = 0.491; <i>p</i> = 0.013) and with W<sub>MAX</sub> enhancement in the EXERCISE group (<i>r</i> = 0.613; <i>p</i> = 0.002).</p> </section> <section> <h3> Conclusions</h3> <p>Our data suggest that annual exercise training has similar clinical efficacy to tripl

{"title":"Long-Term Effects of High-Intensity Aerobic Training on Metabolic Syndrome: An 8-Year Follow-Up Randomized Clinical Trial","authors":"Felix Morales-Palomo, Alfonso Moreno-Cabañas, Laura Alvarez-Jimenez, Diego Mora-Gonzalez, Ricardo Mora-Rodriguez","doi":"10.1002/jcsm.13780","DOIUrl":"https://doi.org/10.1002/jcsm.13780","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Metabolic syndrome (MetS) is a set of five cardiometabolic risk factors that typically worsen with age. One exercise-training programme is effective at improving those factors in middle-aged individuals with MetS. To our knowledge, exercise-training efficacy as MetS individuals age has not been explored. This study determined the effectiveness of a periodized exercise training programme for individuals with MetS after a follow-up period of 8 years.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Forty-seven individuals with MetS were block-randomized into an EXERCISE (<i>n</i> = 22, 52 ± 8 years old, 23% women) or a CONTROL group (<i>n</i> = 25, 53 ± 8 years old, 32% women). Both groups received standard health care, including medical counselling and lifestyle advice at least every 6 months, while participants in EXERCISE also underwent a supervised exercise programme. The intervention lasted 8 years and consisted of 4 months per year (November to March) of high-intensity interval training thrice weekly. At baseline, and after 4 and 8 years of treatment, we assessed body composition, MetS components (i.e., MetS <i>Z</i> score), medication use, cardiorespiratory fitness (CRF; assessed by VO<sub>2MAX</sub>) and maximal leg cycling power output (W<sub>MAX</sub>).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Paradoxically, MetS <i>Z</i> score and body weight were reduced after 8 years (subjects aged from 52 to 60 years old) in both groups (time effect <i>p</i> < 0.001 and <i>p</i> = 0.008; time × group interaction <i>p</i> = 0.253 and <i>p</i> = 0.130). However, in those 8 years, the medicine use score increased threefold in CONTROL (137% increase; from 1.7 to 3.9; <i>p</i> < 0.001) while it did not change in EXERCISE (33%; from 2.0 to 2.7; <i>p</i> = 0.066). In 8 years, CRF and W<sub>MAX</sub> increased in EXERCISE by 14% (3.4 ± 5.6 mL·kg<sup>−1</sup>·min<sup>−1</sup>) and 4% (7 ± 37 W) while decreasing in CONTROL by −7% (−1.6 ± 3.4 mL·kg<sup>−1</sup>·min<sup>−1</sup>) and −14% (−24 ± 27 W) being different between groups after 4 and 8 years (both time × group interaction <i>p</i> = 0.002). Pearson correlations showed that MetS <i>Z</i> score improvements were significantly associated with increases in medication use score in the CONTROL group (<i>r</i> = 0.491; <i>p</i> = 0.013) and with W<sub>MAX</sub> enhancement in the EXERCISE group (<i>r</i> = 0.613; <i>p</i> = 0.002).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>Our data suggest that annual exercise training has similar clinical efficacy to tripl","PeriodicalId":48911,"journal":{"name":"Journal of Cachexia Sarcopenia and Muscle","volume":"16 2","pages":""},"PeriodicalIF":9.4,"publicationDate":"2025-04-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jcsm.13780","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143749855","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: 0

Low Visceral Adipose Tissue Predicts the Outcome of Neoadjuvant Chemotherapy for Colorectal Liver Metastases: A Multicentre Real-World Study

IF 9.4 1区医学 Q1 GERIATRICS & GERONTOLOGY

Journal of Cachexia Sarcopenia and Muscle

Pub Date : 2025-04-01 DOI: 10.1002/jcsm.13785

Yizhen Chen, Hangdong Jia, Rong Ye, Zhenyuan Zhou, Weijie Chen, Ming Zheng, Yuanyuan Zheng

Background

Visceral obesity (VO), associated with excessive visceral adipose tissue (VAT), has been extensively studied in cancer. However, whether low VAT can predict the prognosis of colorectal liver metastases (CRLM) undergoing neoadjuvant chemotherapy (NAC) remains unknown.

Methods

This multicentre real-world cohort study analysed data from initially resectable CRLM patients who received NAC. The predictive effect of VAT on progression-free survival (PFS) and overall survival (OS) was evaluated using restricted cubic splines (RCS). VAT was categorized into low/normal VAT and VO groups using X-tile. The prognostic differences were further assessed through Kaplan–Meier (KM) analysis. The impact of changes in VAT (ΔVAT) after NAC was evaluated.

Results

Among 1524 CRLM patients, 1105 patients (72.51%) were under 65 years old, with a median VAT of 84.00 (36.24–148.00) cm². Of all patients, 804 (52.76%) were female. A U-shaped nonlinear relationship was observed between VAT and both PFS/OS (p < 0.001). Compared with the normal VAT, both low VAT and VO groups showed worsened PFS and OS (p < 0.05). The 3-year PFS rate was 31.6%, 69.0% and 42.0% in the low, normal VAT and VO groups (p < 0.05). The 3-year OS rate was 76.4%, 88.9% and 79.4% in the low, normal VAT and VO groups (p < 0.05). There was also a nonlinear relationship between VAT and NAC-related adverse events, objective response rate and postoperative complications (p < 0.001). An increase in ΔVAT in the low VAT group was associated with better PFS and OS (p < 0.05). In the VO group, both increases and decreases in ΔVAT were associated with worsened PFS and OS (p < 0.05).

Conclusions

This study is the first to reveal that low VAT and VO can predict PFS and OS in CRLM patients undergoing NAC. Baseline VAT and ΔVAT may serve as important indicators for risk stratification and personalized treatment in CRLM patients.

{"title":"Low Visceral Adipose Tissue Predicts the Outcome of Neoadjuvant Chemotherapy for Colorectal Liver Metastases: A Multicentre Real-World Study","authors":"Yizhen Chen, Hangdong Jia, Rong Ye, Zhenyuan Zhou, Weijie Chen, Ming Zheng, Yuanyuan Zheng","doi":"10.1002/jcsm.13785","DOIUrl":"https://doi.org/10.1002/jcsm.13785","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Visceral obesity (VO), associated with excessive visceral adipose tissue (VAT), has been extensively studied in cancer. However, whether low VAT can predict the prognosis of colorectal liver metastases (CRLM) undergoing neoadjuvant chemotherapy (NAC) remains unknown.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>This multicentre real-world cohort study analysed data from initially resectable CRLM patients who received NAC. The predictive effect of VAT on progression-free survival (PFS) and overall survival (OS) was evaluated using restricted cubic splines (RCS). VAT was categorized into low/normal VAT and VO groups using X-tile. The prognostic differences were further assessed through Kaplan–Meier (KM) analysis. The impact of changes in VAT (ΔVAT) after NAC was evaluated.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Among 1524 CRLM patients, 1105 patients (72.51%) were under 65 years old, with a median VAT of 84.00 (36.24–148.00) cm<sup>2</sup>. Of all patients, 804 (52.76%) were female. A U-shaped nonlinear relationship was observed between VAT and both PFS/OS (<i>p</i> < 0.001). Compared with the normal VAT, both low VAT and VO groups showed worsened PFS and OS (<i>p</i> < 0.05). The 3-year PFS rate was 31.6%, 69.0% and 42.0% in the low, normal VAT and VO groups (<i>p</i> < 0.05). The 3-year OS rate was 76.4%, 88.9% and 79.4% in the low, normal VAT and VO groups (<i>p</i> < 0.05). There was also a nonlinear relationship between VAT and NAC-related adverse events, objective response rate and postoperative complications (<i>p</i> < 0.001). An increase in ΔVAT in the low VAT group was associated with better PFS and OS (<i>p</i> < 0.05). In the VO group, both increases and decreases in ΔVAT were associated with worsened PFS and OS (<i>p</i> < 0.05).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>This study is the first to reveal that low VAT and VO can predict PFS and OS in CRLM patients undergoing NAC. Baseline VAT and ΔVAT may serve as important indicators for risk stratification and personalized treatment in CRLM patients.</p>\u0000 </section>\u0000 </div>","PeriodicalId":48911,"journal":{"name":"Journal of Cachexia Sarcopenia and Muscle","volume":"16 2","pages":""},"PeriodicalIF":9.4,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jcsm.13785","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143749622","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: 0

Nuciferine Attenuates Cancer Cachexia-Induced Muscle Wasting in Mice via HSP90AA1

IF 9.4 1区医学 Q1 GERIATRICS & GERONTOLOGY

Journal of Cachexia Sarcopenia and Muscle

Pub Date : 2025-04-01 DOI: 10.1002/jcsm.13777

Xueyan An, Lisha Ma, Yulan Bai, Chaoyue Chen, Ji Liu, Awaguli Dawuti, Kewu Zeng, Baoxue Yang, Bo Han, Abudumijiti Abulizi

<div> <section> <h3> Background</h3> <p>Around 80% of patients with advanced cancer have cancer cachexia (CC), a serious complication for which there are currently no FDA-approved treatments. Nuciferine (NF) is the main active ingredient of lotus leaf, which has anti-inflammatory, anti-tumour and other effects. The purpose of this work was to explore the target and mechanism of NF in preventing cancer cachexia-induced muscle atrophy.</p> </section> <section> <h3> Methods</h3> <p>The action of NF against CC-induced muscle atrophy was determined by constructing an animal model with a series of behavioural tests, H&E staining and related markers. Network pharmacology and molecular docking were used to preliminarily determine the mechanism and targets of NF against CC-induced muscle atrophy. The mechanisms of NF in treating CC-induced muscle atrophy were verified by western blotting. Molecular dynamics simulation (MD), drug affinity responsive target stability (DARTS) and surface plasmon resonance (SPR) were used to validate the key target of NF.</p> </section> <section> <h3> Results</h3> <p>After 13 days of NF treatment, the reduction of limb grip strength and hanging time in LLC model mice increased by 29.7% and 192.2% (<i>p</i> ≤ 0.01; <i>p</i> ≤ 0.001). Gastrocnemius and quadriceps muscles weight/initial body weight (0.98 ± 0.11 and 1.20 ± 0.17) and cross-sectional area of muscle fibres (600–1600 μm<sup>2</sup>) of NF-treated mice were significantly higher than those of the model group (0.84 ± 0.10, 0.94 ± 0.09, 400–800 μm<sup>2</sup>, respectively) (<i>p</i> ≤ 0.01; <i>p</i> ≤ 0.01; <i>p</i> ≤ 0.001). NF treatment also decreased the MyHC (myosin heavy chain) degradation and the protein levels of muscle-specific E3 ubiquitin ligases Atrogin1 and MuRF1 in the model group (<i>p</i> ≤ 0.001; <i>p</i> ≤ 0.01; <i>p</i> ≤ 0.05). Network pharmacology revealed that NF majorly targeted AKT1, TNF and HSP90AA1 to regulate PI3K-Akt and inflammatory pathways. Molecular docking predicted that NF bound best to HSP90AA1. Mechanism analysis demonstrated that NF regulated NF-κB and AKT–mTOR pathways for alleviating muscle wasting in tumour bearing mice. The results of MD, DARTS and SPR further confirmed that HSP90AA1 was the direct target of NF.</p> </section> <section> <h3> Conclusions</h3> <p>Overall, we first discovered that NF retards CC-induced muscle atrophy by regulating AKT–mTOR and NF-κB signalling pathways through directly binding HSP90AA1, suggesting that NF may be an effective treatment for cancer cachexia.</p> </section> <

{"title":"Nuciferine Attenuates Cancer Cachexia-Induced Muscle Wasting in Mice via HSP90AA1","authors":"Xueyan An, Lisha Ma, Yulan Bai, Chaoyue Chen, Ji Liu, Awaguli Dawuti, Kewu Zeng, Baoxue Yang, Bo Han, Abudumijiti Abulizi","doi":"10.1002/jcsm.13777","DOIUrl":"https://doi.org/10.1002/jcsm.13777","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Around 80% of patients with advanced cancer have cancer cachexia (CC), a serious complication for which there are currently no FDA-approved treatments. Nuciferine (NF) is the main active ingredient of lotus leaf, which has anti-inflammatory, anti-tumour and other effects. The purpose of this work was to explore the target and mechanism of NF in preventing cancer cachexia-induced muscle atrophy.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>The action of NF against CC-induced muscle atrophy was determined by constructing an animal model with a series of behavioural tests, H&E staining and related markers. Network pharmacology and molecular docking were used to preliminarily determine the mechanism and targets of NF against CC-induced muscle atrophy. The mechanisms of NF in treating CC-induced muscle atrophy were verified by western blotting. Molecular dynamics simulation (MD), drug affinity responsive target stability (DARTS) and surface plasmon resonance (SPR) were used to validate the key target of NF.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>After 13 days of NF treatment, the reduction of limb grip strength and hanging time in LLC model mice increased by 29.7% and 192.2% (<i>p</i> ≤ 0.01; <i>p</i> ≤ 0.001). Gastrocnemius and quadriceps muscles weight/initial body weight (0.98 ± 0.11 and 1.20 ± 0.17) and cross-sectional area of muscle fibres (600–1600 μm<sup>2</sup>) of NF-treated mice were significantly higher than those of the model group (0.84 ± 0.10, 0.94 ± 0.09, 400–800 μm<sup>2</sup>, respectively) (<i>p</i> ≤ 0.01; <i>p</i> ≤ 0.01; <i>p</i> ≤ 0.001). NF treatment also decreased the MyHC (myosin heavy chain) degradation and the protein levels of muscle-specific E3 ubiquitin ligases Atrogin1 and MuRF1 in the model group (<i>p</i> ≤ 0.001; <i>p</i> ≤ 0.01; <i>p</i> ≤ 0.05). Network pharmacology revealed that NF majorly targeted AKT1, TNF and HSP90AA1 to regulate PI3K-Akt and inflammatory pathways. Molecular docking predicted that NF bound best to HSP90AA1. Mechanism analysis demonstrated that NF regulated NF-κB and AKT–mTOR pathways for alleviating muscle wasting in tumour bearing mice. The results of MD, DARTS and SPR further confirmed that HSP90AA1 was the direct target of NF.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>Overall, we first discovered that NF retards CC-induced muscle atrophy by regulating AKT–mTOR and NF-κB signalling pathways through directly binding HSP90AA1, suggesting that NF may be an effective treatment for cancer cachexia.</p>\u0000 </section>\u0000 <","PeriodicalId":48911,"journal":{"name":"Journal of Cachexia Sarcopenia and Muscle","volume":"16 2","pages":""},"PeriodicalIF":9.4,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jcsm.13777","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143749621","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: 0

Plasma Extracellular Vesicles Biomarkers Linked to Lower Muscle Mass, Function and Physical Performance in Sarcopenia

IF 9.4 1区医学 Q1 GERIATRICS & GERONTOLOGY

Journal of Cachexia Sarcopenia and Muscle

Pub Date : 2025-03-31 DOI: 10.1002/jcsm.13784

Ji Yeon Kim, Tae-Hwan Gil, Hyo Gyeong Lee, Ji-Won Shin, Dong-Hyun Jang, Hyeon Soo Kim, Seung Shin Park, Sang Wan Kim, Chan Soo Shin, Sung Hye Kong, Ok Hee Jeon

<div> <section> <h3> Background</h3> <p>As society ages, identifying individuals at risk of sarcopenia becomes essential. Several plasma biomarkers are used to assess musculoskeletal status, but their results are inconsistent. Extracellular vesicles (EVs) are investigated as disease biomarkers due to their role in transporting molecules and influencing cellular processes. This study investigated the correlation of known sarcopenia biomarkers—adiponectin, myostatin, P3NP, CRP and TNF-α—measured from plasma-derived EVs with muscle mass, function and performance in an Osteoporosis Sarcopenia cohort at the Seoul National University Bundang Hospital.</p> </section> <section> <h3> Methods</h3> <p>Muscle mass was evaluated by measuring appendicular skeletal muscle mass (ASM) using dual X-ray absorptiometry and calculated as ASM/height<sup>2</sup>. Hand grip strength was measured using a hydraulic hand dynamometer for muscle function and physical performance based on the Short Physical Performance Battery (SPPB), walking speed and the five-time-sit-to-stand test. Density gradient ultracentrifugation was used to isolate EVs from the plasma, followed by confirming the expression of sarcopenia biomarkers. Multivariate regression analysis, adjusted for sex, age, body mass index, smoking, drinking, and bone density, was performed.</p> </section> <section> <h3> Results</h3> <p>The mean age of participants was 74.3 ± 12.1 years (range, 52.0–96.0), with 88.2% being female. Plasma-derived EV levels of myostatin and P3NP were significantly associated with walking speed (<i>ꞵ</i> = −0.309, <i>p</i> = 0.014) and SPPB (<i>ꞵ</i> = −0.276, <i>p</i> = 0.029), respectively. TNF-α levels were strongly correlated with hand grip strength (<i>ꞵ</i> = −0.313, <i>p</i> = 0.013). Using receiver-operating characteristic curve analysis, cutoff values for three factors were determined, allowing participants to be categorized into high and low groups. Low myostatin group had a higher hand grip strength (19.63 kg vs. 17.14 kg, <i>p</i> = 0.027) and faster five-time-sit-to-stand test times (17.34 s vs. 23.72 s, <i>p =</i> 0.032). Low P3NP levels showed a stronger grip strength (19.87 kg vs. 16.81 kg, <i>p</i> = 0.008), better SPPB scores (9.10 vs. 8.03, <i>p =</i> 0.006) and five-time-sit-to-stand times (18.31 s vs. 21.87 s, <i>p</i> = 0.002). Low TNF-α levels were linked to better walking speeds (0.82 m/s vs. 0.64 m/s, <i>p</i> = 0.009) and lower SARC-F scores (1.73 vs. 3.26, <i>p</i> = 0.029).</p> </section> <section> <h3> Conclusion</h3> <p>Our research confirmed that EVs-derived my

{"title":"Plasma Extracellular Vesicles Biomarkers Linked to Lower Muscle Mass, Function and Physical Performance in Sarcopenia","authors":"Ji Yeon Kim, Tae-Hwan Gil, Hyo Gyeong Lee, Ji-Won Shin, Dong-Hyun Jang, Hyeon Soo Kim, Seung Shin Park, Sang Wan Kim, Chan Soo Shin, Sung Hye Kong, Ok Hee Jeon","doi":"10.1002/jcsm.13784","DOIUrl":"10.1002/jcsm.13784","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>As society ages, identifying individuals at risk of sarcopenia becomes essential. Several plasma biomarkers are used to assess musculoskeletal status, but their results are inconsistent. Extracellular vesicles (EVs) are investigated as disease biomarkers due to their role in transporting molecules and influencing cellular processes. This study investigated the correlation of known sarcopenia biomarkers—adiponectin, myostatin, P3NP, CRP and TNF-α—measured from plasma-derived EVs with muscle mass, function and performance in an Osteoporosis Sarcopenia cohort at the Seoul National University Bundang Hospital.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Muscle mass was evaluated by measuring appendicular skeletal muscle mass (ASM) using dual X-ray absorptiometry and calculated as ASM/height<sup>2</sup>. Hand grip strength was measured using a hydraulic hand dynamometer for muscle function and physical performance based on the Short Physical Performance Battery (SPPB), walking speed and the five-time-sit-to-stand test. Density gradient ultracentrifugation was used to isolate EVs from the plasma, followed by confirming the expression of sarcopenia biomarkers. Multivariate regression analysis, adjusted for sex, age, body mass index, smoking, drinking, and bone density, was performed.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>The mean age of participants was 74.3 ± 12.1 years (range, 52.0–96.0), with 88.2% being female. Plasma-derived EV levels of myostatin and P3NP were significantly associated with walking speed (<i>ꞵ</i> = −0.309, <i>p</i> = 0.014) and SPPB (<i>ꞵ</i> = −0.276, <i>p</i> = 0.029), respectively. TNF-α levels were strongly correlated with hand grip strength (<i>ꞵ</i> = −0.313, <i>p</i> = 0.013). Using receiver-operating characteristic curve analysis, cutoff values for three factors were determined, allowing participants to be categorized into high and low groups. Low myostatin group had a higher hand grip strength (19.63 kg vs. 17.14 kg, <i>p</i> = 0.027) and faster five-time-sit-to-stand test times (17.34 s vs. 23.72 s, <i>p =</i> 0.032). Low P3NP levels showed a stronger grip strength (19.87 kg vs. 16.81 kg, <i>p</i> = 0.008), better SPPB scores (9.10 vs. 8.03, <i>p =</i> 0.006) and five-time-sit-to-stand times (18.31 s vs. 21.87 s, <i>p</i> = 0.002). Low TNF-α levels were linked to better walking speeds (0.82 m/s vs. 0.64 m/s, <i>p</i> = 0.009) and lower SARC-F scores (1.73 vs. 3.26, <i>p</i> = 0.029).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>Our research confirmed that EVs-derived my","PeriodicalId":48911,"journal":{"name":"Journal of Cachexia Sarcopenia and Muscle","volume":"16 2","pages":""},"PeriodicalIF":9.4,"publicationDate":"2025-03-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jcsm.13784","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143737017","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: 0

Balancing LncRNA H19 and miR-675 Bioconversion as a Key Regulator of Embryonic Myogenesis Under Maternal Obesity

IF 9.4 1区医学 Q1 GERIATRICS & GERONTOLOGY

Journal of Cachexia Sarcopenia and Muscle

Pub Date : 2025-03-31 DOI: 10.1002/jcsm.13791

Yao Gao, Md Nazmul Hossain, Liang Zhao, Xiangdong Liu, Yanting Chen, Jeanene Marie Deavila, Mei-Jun Zhu, Gordon K. Murdoch, Min Du

<div> <section> <h3> Background</h3> <p>Maternal obesity (MO) impairs fetal skeletal muscle development, but the underlying mechanisms remain poorly defined. The regulatory roles of lncRNA <i>H19</i> and its first exon derived <i>microRNA675</i> (<i>miR675</i>) in prenatal muscle development remain to be examined. <i>H19</i>/<i>Igf2</i> are in the same imprinting cluster with <i>H19</i> expressed from the maternal allele while <i>Igf2</i> expresses paternally. <i>H19</i> contains a G-rich loop, and KH-type splicing regulatory protein (KHSRP) mediates the biogenesis of pre-<i>miRNAs</i> containing G-rich loops, which depends on its phosphorylation by AKT, a key mediator of IGF2 signalling. This study aims to depict the elusive function of these regulators that are affected by MO during embryonic myogenesis.</p> </section> <section> <h3> Methods</h3> <p>Single-cell transcriptomic sequencing and GeoMx spatial RNA sequencing were performed to identify the differentially expressed genes between embryos from MO and control (CT) mice. Both E11.5 and E13.5 embryos were collected and analysed to validate the sequencing data. The roles of <i>H19</i> and <i>miR657</i> in myogenesis were further analysed in P19 embryonic cells via CRISPR/dCas9-mediated <i>H19</i> activation and inhibition. The epigenetic changes of <i>H19</i> were analysed by methylated DNA immunoprecipitation, and allele-targeted analysis of <i>H19</i> was performed by crossing C57BL/6J and CAST/EiJ mice.</p> </section> <section> <h3> Results</h3> <p>Transcriptomic analysis showed that MO embryos contained less differentiated myocytes (1.34%) than CT embryos (2.86%). Myogenesis-related GO biological processes were down-regulated in the MO embryonic myotome region. MO embryos showed lower expression of myogenic transcription factors such as <i>Myf5</i>, <i>Myod1</i>, <i>Myog</i>, <i>Mef2c</i> and <i>Myh3</i> (<i>p</i> < 0.05). MO altered epigenetic modifications of the <i>H19</i> genomic cluster, showing a decreased methylation level in <i>H19</i> imprinting control region (<i>p <</i> 0.05) and a diallelic expression pattern of <i>H19</i>, which elevated its expression in MO embryos. Overexpression of <i>H19</i> inhibited myogenesis in P19 cells, but <i>miR675</i> promoted myogenesis, suggesting the critical regulatory roles of bioconversion of <i>H19</i> to <i>miR675</i>. A KHSRP mediates the biogenesis of <i>miR675</i>, a process that relies on its phosphorylation by IGF2/AKT signalling. Knocking-down of KHSRP and inhibition of AKT abolished <i>miR675</i> biogenesis. MO suppressed IGF2/AKT signalling and blocked KHSRP-dependent <i>miR675</i> biogenesis in embryos.</p> </

{"title":"Balancing LncRNA H19 and miR-675 Bioconversion as a Key Regulator of Embryonic Myogenesis Under Maternal Obesity","authors":"Yao Gao, Md Nazmul Hossain, Liang Zhao, Xiangdong Liu, Yanting Chen, Jeanene Marie Deavila, Mei-Jun Zhu, Gordon K. Murdoch, Min Du","doi":"10.1002/jcsm.13791","DOIUrl":"10.1002/jcsm.13791","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Maternal obesity (MO) impairs fetal skeletal muscle development, but the underlying mechanisms remain poorly defined. The regulatory roles of lncRNA <i>H19</i> and its first exon derived <i>microRNA675</i> (<i>miR675</i>) in prenatal muscle development remain to be examined. <i>H19</i>/<i>Igf2</i> are in the same imprinting cluster with <i>H19</i> expressed from the maternal allele while <i>Igf2</i> expresses paternally. <i>H19</i> contains a G-rich loop, and KH-type splicing regulatory protein (KHSRP) mediates the biogenesis of pre-<i>miRNAs</i> containing G-rich loops, which depends on its phosphorylation by AKT, a key mediator of IGF2 signalling. This study aims to depict the elusive function of these regulators that are affected by MO during embryonic myogenesis.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Single-cell transcriptomic sequencing and GeoMx spatial RNA sequencing were performed to identify the differentially expressed genes between embryos from MO and control (CT) mice. Both E11.5 and E13.5 embryos were collected and analysed to validate the sequencing data. The roles of <i>H19</i> and <i>miR657</i> in myogenesis were further analysed in P19 embryonic cells via CRISPR/dCas9-mediated <i>H19</i> activation and inhibition. The epigenetic changes of <i>H19</i> were analysed by methylated DNA immunoprecipitation, and allele-targeted analysis of <i>H19</i> was performed by crossing C57BL/6J and CAST/EiJ mice.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Transcriptomic analysis showed that MO embryos contained less differentiated myocytes (1.34%) than CT embryos (2.86%). Myogenesis-related GO biological processes were down-regulated in the MO embryonic myotome region. MO embryos showed lower expression of myogenic transcription factors such as <i>Myf5</i>, <i>Myod1</i>, <i>Myog</i>, <i>Mef2c</i> and <i>Myh3</i> (<i>p</i> < 0.05). MO altered epigenetic modifications of the <i>H19</i> genomic cluster, showing a decreased methylation level in <i>H19</i> imprinting control region (<i>p <</i> 0.05) and a diallelic expression pattern of <i>H19</i>, which elevated its expression in MO embryos. Overexpression of <i>H19</i> inhibited myogenesis in P19 cells, but <i>miR675</i> promoted myogenesis, suggesting the critical regulatory roles of bioconversion of <i>H19</i> to <i>miR675</i>. A KHSRP mediates the biogenesis of <i>miR675</i>, a process that relies on its phosphorylation by IGF2/AKT signalling. Knocking-down of KHSRP and inhibition of AKT abolished <i>miR675</i> biogenesis. MO suppressed IGF2/AKT signalling and blocked KHSRP-dependent <i>miR675</i> biogenesis in embryos.</p>\u0000 </","PeriodicalId":48911,"journal":{"name":"Journal of Cachexia Sarcopenia and Muscle","volume":"16 2","pages":""},"PeriodicalIF":9.4,"publicationDate":"2025-03-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jcsm.13791","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143737016","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: 0

A Causal Effect of Serum 25(OH)D Level on Appendicular Muscle Mass: Evidence From NHANES Data and Mendelian Randomization Analyses

IF 9.4 1区医学 Q1 GERIATRICS & GERONTOLOGY

Journal of Cachexia Sarcopenia and Muscle

Pub Date : 2025-03-31 DOI: 10.1002/jcsm.13778

Qian Ren, Jinrong Liang, Yanmei Su, Ruijing Tian, Junxian Wu, Sheng Ge, Peizhan Chen

<div> <section> <h3> Background</h3> <p>Low serum vitamin D status was reported to be associated with reduced muscle mass; however, it is inconclusive whether this relationship is causal. This study used data from the National Health and Nutrition Examination Survey (NHANES) and two-sample Mendelian randomization (MR) analyses to ascertain the causal relationship between serum 25-hydroxyvitamin D [25(OH)D] and appendicular muscle mass (AMM).</p> </section> <section> <h3> Methods</h3> <p>In the NHANES 2011–2018 dataset, 11 242 participants (5588 males and 5654 females) aged 18–59 years old were included, and multivariant linear regression was performed to assess the relationship between 25(OH)D and AMM measured by dual-energy X-ray absorptiometry. In two-sample MR analysis, 167 single nucleotide polymorphisms significantly associated with serum 25(OH)D at the genome-wide association level (<i>p</i> < 5 × 10<sup>−8</sup>) were applied as instrumental variables (IVs) to assess vitamin D effects on AMM in the UK Biobank (417 580 Europeans) using univariable and multivariable MR (MVMR) models.</p> </section> <section> <h3> Results</h3> <p>In the NHANES dataset, serum 25(OH)D concentrations were positively associated with AMM (<i>β</i> = 0.013, SE = 0.001, <i>p</i> < 0.001) in all participants, after adjustment for age, race, season of blood collection, education, income, body mass index and physical activity. In stratification analysis by sex, males (<i>β</i> = 0.024, SE = 0.002, <i>p</i> < 0.001) showed more pronounced positive associations than females (<i>β</i> = 0.003, SE = 0.002, <i>p</i> = 0.024). In univariable MR, genetically higher serum 25(OH)D levels were positively associated with AMM in all participants (<i>β</i> = 0.049, SE = 0.024, <i>p</i> = 0.039) and males (<i>β</i> = 0.057, SE = 0.025, <i>p</i> = 0.021), but only marginally significant in females (<i>β</i> = 0.043, SE = 0.025, <i>p</i> = 0.090) based on IVW models was noticed. No significant pleiotropy effects were detected for the IVs in the two-sample MR investigations. In MVMR analysis, a positive causal effect of 25(OH)D on AMM was observed in the total population (<i>β</i> = 0.116, SE = 0.051, <i>p</i> = 0.022), males (<i>β</i> = 0.111, SE = 0.053, <i>p</i> = 0.036) and females (<i>β</i> = 0.124, SE = 0.054, <i>p</i> = 0.021).</p> </section> <section> <h3> Conclusions</h3> <p>Our results suggested a positive causal effect of serum 25(OH)D concentration on AMM; however, more researches are warranted to unveil the underlying biological mechanisms and evaluate the effects o

{"title":"A Causal Effect of Serum 25(OH)D Level on Appendicular Muscle Mass: Evidence From NHANES Data and Mendelian Randomization Analyses","authors":"Qian Ren, Jinrong Liang, Yanmei Su, Ruijing Tian, Junxian Wu, Sheng Ge, Peizhan Chen","doi":"10.1002/jcsm.13778","DOIUrl":"10.1002/jcsm.13778","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Low serum vitamin D status was reported to be associated with reduced muscle mass; however, it is inconclusive whether this relationship is causal. This study used data from the National Health and Nutrition Examination Survey (NHANES) and two-sample Mendelian randomization (MR) analyses to ascertain the causal relationship between serum 25-hydroxyvitamin D [25(OH)D] and appendicular muscle mass (AMM).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>In the NHANES 2011–2018 dataset, 11 242 participants (5588 males and 5654 females) aged 18–59 years old were included, and multivariant linear regression was performed to assess the relationship between 25(OH)D and AMM measured by dual-energy X-ray absorptiometry. In two-sample MR analysis, 167 single nucleotide polymorphisms significantly associated with serum 25(OH)D at the genome-wide association level (<i>p</i> < 5 × 10<sup>−8</sup>) were applied as instrumental variables (IVs) to assess vitamin D effects on AMM in the UK Biobank (417 580 Europeans) using univariable and multivariable MR (MVMR) models.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>In the NHANES dataset, serum 25(OH)D concentrations were positively associated with AMM (<i>β</i> = 0.013, SE = 0.001, <i>p</i> < 0.001) in all participants, after adjustment for age, race, season of blood collection, education, income, body mass index and physical activity. In stratification analysis by sex, males (<i>β</i> = 0.024, SE = 0.002, <i>p</i> < 0.001) showed more pronounced positive associations than females (<i>β</i> = 0.003, SE = 0.002, <i>p</i> = 0.024). In univariable MR, genetically higher serum 25(OH)D levels were positively associated with AMM in all participants (<i>β</i> = 0.049, SE = 0.024, <i>p</i> = 0.039) and males (<i>β</i> = 0.057, SE = 0.025, <i>p</i> = 0.021), but only marginally significant in females (<i>β</i> = 0.043, SE = 0.025, <i>p</i> = 0.090) based on IVW models was noticed. No significant pleiotropy effects were detected for the IVs in the two-sample MR investigations. In MVMR analysis, a positive causal effect of 25(OH)D on AMM was observed in the total population (<i>β</i> = 0.116, SE = 0.051, <i>p</i> = 0.022), males (<i>β</i> = 0.111, SE = 0.053, <i>p</i> = 0.036) and females (<i>β</i> = 0.124, SE = 0.054, <i>p</i> = 0.021).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>Our results suggested a positive causal effect of serum 25(OH)D concentration on AMM; however, more researches are warranted to unveil the underlying biological mechanisms and evaluate the effects o","PeriodicalId":48911,"journal":{"name":"Journal of Cachexia Sarcopenia and Muscle","volume":"16 2","pages":""},"PeriodicalIF":9.4,"publicationDate":"2025-03-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jcsm.13778","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143737071","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: 0

Longitudinal Cohort Study Investigating Fall Risk Across Diverse Muscle Health Statuses Among Older People in the Community

IF 9.4 1区医学 Q1 GERIATRICS & GERONTOLOGY

Journal of Cachexia Sarcopenia and Muscle

Pub Date : 2025-03-31 DOI: 10.1002/jcsm.13788

Yuan-Ping Chao, Wen-Hui Fang, Tao-Chun Peng, Li-Wei Wu, Hui-Fang Yang, Tung-Wei Kao

<div> <section> <h3> Background</h3> <p>Falls constitute a significant public health concern among older adults, particularly those with diminished muscle health integrity. The relative contributions of reduced muscle mass versus impaired muscle function to fall risk remain debated. Discrepant conclusions in previous studies exist due to divergent muscle health categorizations and parameter measurements. This study investigated longitudinal risk of falls across a spectrum of muscle health statuses among older people in the community.</p> </section> <section> <h3> Methods</h3> <p>Community-dwelling participants aged 65 years and older, undergoing annual health assessments, were enrolled between 2015 and 2023. Measurements included handgrip strength, walking speed and appendicular skeletal muscle mass. Dynapenia was defined as impaired muscle function with preserved muscle mass, presarcopenia was characterized as reduced muscle mass with maintained muscle function, and sarcopenia was identified as concurrent losses in both muscle mass and muscle function. Older people with normal muscle mass and muscle function were defined as having a robust muscle health status. Participants without a history of falls at baseline were monitored continuously and were censored if a fall incident was recorded during later yearly assessment. Kaplan–Meier and Cox regression analyses were used to compare fall risk across different muscle health statuses.</p> </section> <section> <h3> Results</h3> <p>The final analysis included a total of 863 participants with a mean age of 71.93 ± 6.62 years, and 57.58% were female. Compared with the other groups, the dynapenic group exhibited a lower physical activity, greater body mass index and slower gait speed. The participants with dynapenia experienced the highest fall incidence (27.15%). The hazard ratios (HRs) for fall were 2.65 (95% confidence interval [CI] = 1.72–4.08, <i>p</i> < 0.001) for dynapenia, 1.54 (95% CI = 0.92–2.57, <i>p</i> = 0.095) for presarcopenia and 1.87 (95% CI = 1.04–3.33, <i>p</i> = 0.034) for sarcopenia. After adjustment for multiple covariates, the fall risk remained significantly greater in the dynapenic group (HR = 2.10, 95% CI = 1.28–3.43, <i>p</i> = 0.003) than in the sarcopenic group (HR = 1.31, 95% CI = 0.69–2.46, <i>p</i> = 0.402). Female dynapenic participants with coronary artery disease, arthritis and sedative agent use had a high fall risk, especially those with two or more risk factors (HR = 2.82, 95%CI = 1.37–5.82, <i>p</i> = 0.005).</p> </section> <section> <h3> Conclusions</h3> <p>Older

{"title":"Longitudinal Cohort Study Investigating Fall Risk Across Diverse Muscle Health Statuses Among Older People in the Community","authors":"Yuan-Ping Chao, Wen-Hui Fang, Tao-Chun Peng, Li-Wei Wu, Hui-Fang Yang, Tung-Wei Kao","doi":"10.1002/jcsm.13788","DOIUrl":"10.1002/jcsm.13788","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Falls constitute a significant public health concern among older adults, particularly those with diminished muscle health integrity. The relative contributions of reduced muscle mass versus impaired muscle function to fall risk remain debated. Discrepant conclusions in previous studies exist due to divergent muscle health categorizations and parameter measurements. This study investigated longitudinal risk of falls across a spectrum of muscle health statuses among older people in the community.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Community-dwelling participants aged 65 years and older, undergoing annual health assessments, were enrolled between 2015 and 2023. Measurements included handgrip strength, walking speed and appendicular skeletal muscle mass. Dynapenia was defined as impaired muscle function with preserved muscle mass, presarcopenia was characterized as reduced muscle mass with maintained muscle function, and sarcopenia was identified as concurrent losses in both muscle mass and muscle function. Older people with normal muscle mass and muscle function were defined as having a robust muscle health status. Participants without a history of falls at baseline were monitored continuously and were censored if a fall incident was recorded during later yearly assessment. Kaplan–Meier and Cox regression analyses were used to compare fall risk across different muscle health statuses.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>The final analysis included a total of 863 participants with a mean age of 71.93 ± 6.62 years, and 57.58% were female. Compared with the other groups, the dynapenic group exhibited a lower physical activity, greater body mass index and slower gait speed. The participants with dynapenia experienced the highest fall incidence (27.15%). The hazard ratios (HRs) for fall were 2.65 (95% confidence interval [CI] = 1.72–4.08, <i>p</i> < 0.001) for dynapenia, 1.54 (95% CI = 0.92–2.57, <i>p</i> = 0.095) for presarcopenia and 1.87 (95% CI = 1.04–3.33, <i>p</i> = 0.034) for sarcopenia. After adjustment for multiple covariates, the fall risk remained significantly greater in the dynapenic group (HR = 2.10, 95% CI = 1.28–3.43, <i>p</i> = 0.003) than in the sarcopenic group (HR = 1.31, 95% CI = 0.69–2.46, <i>p</i> = 0.402). Female dynapenic participants with coronary artery disease, arthritis and sedative agent use had a high fall risk, especially those with two or more risk factors (HR = 2.82, 95%CI = 1.37–5.82, <i>p</i> = 0.005).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>Older ","PeriodicalId":48911,"journal":{"name":"Journal of Cachexia Sarcopenia and Muscle","volume":"16 2","pages":""},"PeriodicalIF":9.4,"publicationDate":"2025-03-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jcsm.13788","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143736878","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: 0

Transcriptional Co-Activator With PDZ Binding Motif (TAZ) Inhibits Dexamethasone-Induced Muscle Atrophy via mTOR Signalling

IF 9.4 1区医学 Q1 GERIATRICS & GERONTOLOGY

Journal of Cachexia Sarcopenia and Muscle

Pub Date : 2025-03-30 DOI: 10.1002/jcsm.13790

Kyung Min Kim, Ho Taek Oh, Youjin Do, Gi Don Yoo, Woong Heo, Jeekeon Park, Hyejin Yang, Suh Jin Yoon, Mi Ran Byun, Eun Sook Hwang, Jeong-Ho Hong

Background

Glucocorticoid therapy has a beneficial effect in several diseases, but chronic treatment has adverse effects, including muscle atrophy, which refers to the gradual decrease in muscle mass, size and strength. It is important to know how the muscle atrophy occurs, but the underlying mechanism is not yet fully understood. This study shows that dexamethasone decreases levels of the transcriptional co-activator with PDZ binding motif (TAZ), which facilitates dexamethasone-induced muscle atrophy.

Methods

To induce muscle atrophy, C2C12 myotubes were treated with dexamethasone, and mice were fed with water containing dexamethasone. Muscle atrophy was analysed for the expression of myosin heavy chain, MuRF1 and Atrogin-1 using immunofluorescence staining, immunoblot analysis and qRT-PCR. Muscle tissue was analysed by haematoxylin and eosin staining. Adeno-associated virus was used for overexpression of wild-type and mutant TAZ.

Results

TAZ levels decrease in dexamethasone-treated mice (0.36-fold, p < 0.001) and C2C12 myotubes (0.44-fold, p = 0.024). Overexpression of the TAZ mutant, which resists its proteolytic degradation, inhibits dexamethasone-induced muscle atrophy. Atrogin-1 and MuRF1 interact with TAZ and facilitate its degradation in dexamethasone-treated C2C12 myotubes. TAZ mutant stimulates protein synthesis through activation of mTOR signalling via induction of RhebL1 (DEX; Con vs, TAZ4SA: 5.1-fold, p < 0.001) in dexamethasone-treated mice. Ginsenoside Rb3 increases TAZ levels in dexamethasone-treated mice (1.49-fold, p = 0.007) and C2C12 myotubes (1.63-fold, p = 0.01), which stimulates mTOR signalling and inhibits dexamethasone-induced muscle atrophy.

Conclusions

Our results demonstrate a novel regulatory mechanism of dexamethasone-induced muscle atrophy by TAZ, suggesting that stabilisation of TAZ in muscle cells ameliorates the muscle atrophy. These results suggest that TAZ may be a drug target for the dexamethasone-induced muscle atrophy.

{"title":"Transcriptional Co-Activator With PDZ Binding Motif (TAZ) Inhibits Dexamethasone-Induced Muscle Atrophy via mTOR Signalling","authors":"Kyung Min Kim, Ho Taek Oh, Youjin Do, Gi Don Yoo, Woong Heo, Jeekeon Park, Hyejin Yang, Suh Jin Yoon, Mi Ran Byun, Eun Sook Hwang, Jeong-Ho Hong","doi":"10.1002/jcsm.13790","DOIUrl":"10.1002/jcsm.13790","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Glucocorticoid therapy has a beneficial effect in several diseases, but chronic treatment has adverse effects, including muscle atrophy, which refers to the gradual decrease in muscle mass, size and strength. It is important to know how the muscle atrophy occurs, but the underlying mechanism is not yet fully understood. This study shows that dexamethasone decreases levels of the transcriptional co-activator with PDZ binding motif (TAZ), which facilitates dexamethasone-induced muscle atrophy.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>To induce muscle atrophy, C2C12 myotubes were treated with dexamethasone, and mice were fed with water containing dexamethasone. Muscle atrophy was analysed for the expression of myosin heavy chain, MuRF1 and Atrogin-1 using immunofluorescence staining, immunoblot analysis and qRT-PCR. Muscle tissue was analysed by haematoxylin and eosin staining. Adeno-associated virus was used for overexpression of wild-type and mutant TAZ.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>TAZ levels decrease in dexamethasone-treated mice (0.36-fold, <i>p</i> < 0.001) and C2C12 myotubes (0.44-fold, <i>p</i> = 0.024). Overexpression of the TAZ mutant, which resists its proteolytic degradation, inhibits dexamethasone-induced muscle atrophy. Atrogin-1 and MuRF1 interact with TAZ and facilitate its degradation in dexamethasone-treated C2C12 myotubes. TAZ mutant stimulates protein synthesis through activation of mTOR signalling via induction of RhebL1 (DEX; Con vs, TAZ4SA: 5.1-fold, <i>p</i> < 0.001) in dexamethasone-treated mice. Ginsenoside Rb3 increases TAZ levels in dexamethasone-treated mice (1.49-fold, <i>p</i> = 0.007) and C2C12 myotubes (1.63-fold, <i>p</i> = 0.01), which stimulates mTOR signalling and inhibits dexamethasone-induced muscle atrophy.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>Our results demonstrate a novel regulatory mechanism of dexamethasone-induced muscle atrophy by TAZ, suggesting that stabilisation of TAZ in muscle cells ameliorates the muscle atrophy. These results suggest that TAZ may be a drug target for the dexamethasone-induced muscle atrophy.</p>\u0000 </section>\u0000 </div>","PeriodicalId":48911,"journal":{"name":"Journal of Cachexia Sarcopenia and Muscle","volume":"16 2","pages":""},"PeriodicalIF":9.4,"publicationDate":"2025-03-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jcsm.13790","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143737015","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: 0

Body Composition Assessment Provides Prognostic Information in Patients With Cancer Affected by Chronic Graft vs. Host Disease

IF 9.4 1区医学 Q1 GERIATRICS & GERONTOLOGY

Journal of Cachexia Sarcopenia and Muscle

Pub Date : 2025-03-28 DOI: 10.1002/jcsm.13759

Asmita Mishra, Ram Thapa, Kevin Bigam, Martine Extermann, Rawan Faramand, Farhad Khimani, Xuefeng Wang, Vickie Baracos, Joseph A. Pidala

<div> <section> <h3> Background</h3> <p>Additional tools are needed to assess mortality risk among patients with cancer. Patients with chronic graft vs. host disease (cGVHD) after allogeneic haematopoietic cell transplantation (HCT) represent a high-risk cancer population with mortality risk explained by cGVHD severity, but also informed by baseline comorbidities, functional status before and after HCT, and cumulative toxicity from the procedure and its complications. Radiographic body composition metrics from CT scans have previously shown association with complications in other populations.</p> </section> <section> <h3> Methods</h3> <p>We examined a single-centre consecutive series (2005–2016) of HCT recipients with cGVHD and CT-scans immediately proximal to cGVHD diagnosis to investigate association of radiographic body composition measures and mortality. Skeletal muscle index (SMI) and fat index (FI) were quantified on CT imaging at the 3rd lumbar (L3) and 4th thoracic (T4) vertebra. SM Hounsfield units (HU) were obtained to evaluate SM density. Cut points for SMI were from literature and cut points for FI were established by sex-specific optimal stratification.</p> </section> <section> <h3> Results</h3> <p>A total of <i>n</i> = 113 patients met the inclusion criteria for this analysis, aged 51.2 ± 10.5(SD) years and predominantly male (<i>n</i> = 71, 63%) and diagnosed with NHL (<i>n</i> = 110, 97%). Onset cGVHD NIH overall severity was mild in <i>N</i> = 56 (49%), moderate in 44 (38%) and severe in 15 (13%), with median time to cGVHD onset after HCT of 173 days [IQR 122;295]. A CT scan at 77 days [IQR 33;202] post HCT was selected for analysis. In multivariate analysis, CT-defined body fat ≥ 35% was independently associated with increased mortality (HR 2.094 (95% CI 1.060, 4.136), <i>p</i> = 0.033) overall. Patients of male sex had higher FI than females and showed a more prominent association between high FI and mortality. SMI as well as other indices of adiposity were not associated with survival in multivariable analysis including BMI, sarcopenic obesity and low skeletal muscle radiodensity. In exploratory analyses, we demonstrated similar results per CT chest at T4, suggesting possible future application to a larger HCT population.</p> </section> <section> <h3> Conclusions</h3> <p>These data support that radiographic body composition measures provide prognostic information among patients with cancer affected by cGVHD post-HCT and suggest that high body fat % is a promising candidate for future study. These findings suggest that low skelet

{"title":"Body Composition Assessment Provides Prognostic Information in Patients With Cancer Affected by Chronic Graft vs. Host Disease","authors":"Asmita Mishra, Ram Thapa, Kevin Bigam, Martine Extermann, Rawan Faramand, Farhad Khimani, Xuefeng Wang, Vickie Baracos, Joseph A. Pidala","doi":"10.1002/jcsm.13759","DOIUrl":"https://doi.org/10.1002/jcsm.13759","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Additional tools are needed to assess mortality risk among patients with cancer. Patients with chronic graft vs. host disease (cGVHD) after allogeneic haematopoietic cell transplantation (HCT) represent a high-risk cancer population with mortality risk explained by cGVHD severity, but also informed by baseline comorbidities, functional status before and after HCT, and cumulative toxicity from the procedure and its complications. Radiographic body composition metrics from CT scans have previously shown association with complications in other populations.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>We examined a single-centre consecutive series (2005–2016) of HCT recipients with cGVHD and CT-scans immediately proximal to cGVHD diagnosis to investigate association of radiographic body composition measures and mortality. Skeletal muscle index (SMI) and fat index (FI) were quantified on CT imaging at the 3rd lumbar (L3) and 4th thoracic (T4) vertebra. SM Hounsfield units (HU) were obtained to evaluate SM density. Cut points for SMI were from literature and cut points for FI were established by sex-specific optimal stratification.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>A total of <i>n</i> = 113 patients met the inclusion criteria for this analysis, aged 51.2 ± 10.5(SD) years and predominantly male (<i>n</i> = 71, 63%) and diagnosed with NHL (<i>n</i> = 110, 97%). Onset cGVHD NIH overall severity was mild in <i>N</i> = 56 (49%), moderate in 44 (38%) and severe in 15 (13%), with median time to cGVHD onset after HCT of 173 days [IQR 122;295]. A CT scan at 77 days [IQR 33;202] post HCT was selected for analysis. In multivariate analysis, CT-defined body fat ≥ 35% was independently associated with increased mortality (HR 2.094 (95% CI 1.060, 4.136), <i>p</i> = 0.033) overall. Patients of male sex had higher FI than females and showed a more prominent association between high FI and mortality. SMI as well as other indices of adiposity were not associated with survival in multivariable analysis including BMI, sarcopenic obesity and low skeletal muscle radiodensity. In exploratory analyses, we demonstrated similar results per CT chest at T4, suggesting possible future application to a larger HCT population.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>These data support that radiographic body composition measures provide prognostic information among patients with cancer affected by cGVHD post-HCT and suggest that high body fat % is a promising candidate for future study. These findings suggest that low skelet","PeriodicalId":48911,"journal":{"name":"Journal of Cachexia Sarcopenia and Muscle","volume":"16 2","pages":""},"PeriodicalIF":9.4,"publicationDate":"2025-03-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jcsm.13759","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143717182","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: 0

Correction to “The Prevalence Patterns and Risk Factor Profiles of Poor Muscle Health and Its Associated Components in Multi-Ethnic Older Asians: The PIONEER Study”

IF 9.4 1区医学 Q1 GERIATRICS & GERONTOLOGY

Journal of Cachexia Sarcopenia and Muscle

Pub Date : 2025-03-27 DOI: 10.1002/jcsm.13774

Gupta, P, Vu, TA, Man, REK, et al., The prevalence patterns and risk factor profiles of poor muscle health and its associated components in multiethnic older Asians: The PIONEER study. Journal of cachexia, sarcopenia and muscle. Aug 2024; 15(4): 1376–1387. doi:10.1002/jcsm.13483

In the Funding ‘section’, we would like to add: “This research is supported by the National Medical Research Council (NMRC) through the SingHealth PULSES II Centre Grant (CG21APR1013).” After this sentence, it continues to read: “The grant body had no roles in design, conduct or data analysis of the study, nor in manuscript preparation and approval.”

We apologize for this error.

引用次数: 0