Journal of Cachexia, Sarcopenia and Muscle最新文献

{"title":"Comment on ‘Allograft function and muscle mass evolution after kidney transplantation’ by Gaillard et al.","authors":"Thomas Stehlé,&nbsp;Antoine Morel,&nbsp;Yaniss Ouamri,&nbsp;Frédéric Pigneur","doi":"10.1002/jcsm.13203","DOIUrl":"https://doi.org/10.1002/jcsm.13203","url":null,"abstract":"<p>We read with interest the article by Gaillard et al., entitled ‘Allograft function and muscle mass evolution after kidney transplantation’.<span>¹</span> This article highlights the association between measured glomerular filtration rate (mGFR) and urinary creatinine excretion rate (CER) at 3 months and 1 year after kidney transplantation (KT) and the association between CER and mortality in kidney transplant recipients (KTr). We previously investigated, in a population of 200 KTr, the prevalence and consequences of disturbances of muscle parameters assessed on an unenhanced cross-sectional CT-scan taken at the level of the third lumbar vertebra.<span>²</span> We had determined age-specific and sex-specific normality thresholds on 130 healthy subjects. Twenty-five per cent of KTr had a muscle density below the 2.5th percentile of the reference population. Myosteatosis thus defined was independently associated with mortality. Conversely, in our study, only 5% of KTr had a skeletal muscle mass index (SMI) below the 2.5th percentile of the reference population, and these few patients had no apparent increased risk of mortality.</p><p>The discrepancy between the results of these two studies may be explained by differences in the methods used to estimate skeletal muscle mass. Although SMI is adjusted for height squared, the authors did not adjust CER for body size. This may account for the unbalanced distribution of women in the lowest tertile of CER, with patients in this group being also older, and smaller. Although the authors subsequently incorporated morphometric parameters into the multivariate analyses, their methodological choice to use a muscle mass-derived variable, namely, the CER, without adjustment for height may have impacted their results.</p><p>Comparison of muscle mass assessed by CER or by methods based on CT-scan segmentation, with or without adjustment for body size, is therefore of interest for the aim of standardizing clinical practice.</p><p>In 127 of the 130 healthy subjects in our study, CER had been measured from four timed periods of 40 min. We investigated in these patients both the correlation and agreement between CER and SMI, CER and total lumbar muscle cross-sectional area at the third vertebra (MCSA) and then between CER and the product of MCSA by height. Because the latter provides a muscle volume rather than a muscle surface area, we hypothesized that MCSA × height could be a better surrogate marker of total muscle mass. We used the Pearson test to assess the correlation between the variables. Agreement was assessed both by Fleiss' kappa coefficient, and by calculating the proportion of patients classified in the same tertiles between the variables of interest.</p><p>The Pearson correlation coefficients were 0.723, 0.890 and 0.910 in the correlation analyses between CER and SMI, MCSA and MCSA × height, respectively (<i>Figure</i> 1). 64%, 81% and 93% of patients were classified in the same te","PeriodicalId":186,"journal":{"name":"Journal of Cachexia, Sarcopenia and Muscle","volume":"14 2","pages":"1139-1141"},"PeriodicalIF":8.9,"publicationDate":"2023-03-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jcsm.13203","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"6104619","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The association between weight change after gastric cancer surgery and type 2 diabetes risk: A nationwide cohort study","authors":"Yeongkeun Kwon,&nbsp;Jane Ha,&nbsp;Dohyang Kim,&nbsp;Jinseub Hwang,&nbsp;Shin-Hoo Park,&nbsp;Jin-Won Kwon,&nbsp;Sungsoo Park","doi":"10.1002/jcsm.13206","DOIUrl":"https://doi.org/10.1002/jcsm.13206","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Although gastric cancer patients generally experience drastic weight decrease post-gastrectomy, the impact of weight decrease on type 2 diabetes risk remains unclear. We investigated the type 2 diabetes risk after gastric cancer surgery according to postoperative weight decrease in gastric cancer survivors in South Korea, the country with the world's highest rate of gastric cancer survival.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>This retrospective nationwide cohort study included gastric cancer surgery recipients between 2004 and 2014 who survived for ≥5 years post-surgery. We included patients without a history of diabetes at the time of surgery and those who had not received adjuvant chemotherapy before or after the surgery. Postoperative weight loss was defined as the per cent body weight loss at 3 years post-surgery compared with the baseline. The type 2 diabetes risk was evaluated using Cox regression analyses for five groups of postoperative weight decrease.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>In 5618 included gastric cancer surgery recipients (mean age, 55.7 [standard deviation, SD, 10.9] years; 21.9% female; mean body mass index, 23.7 [SD, 2.9] kg/m²), 331 patients (5.9%) developed postoperative type 2 diabetes during follow-up duration of 8.1 years (median; interquartile range, 4.8 years; maximum, 15.2 years). Compared with those who gained weight post-surgery, patients with ≥ −15% to &lt; −10% of postoperative weight decrease (hazard ratio, 0.65; 95% confidence interval, 0.49–0.87; <i>P</i> = 0.004) had the lowest type 2 diabetes risk. A non-linear association occurred between postoperative weight decrease and the type 2 diabetes risk in gastrectomy recipients (Akaike's information criterion [AIC] for non-linear model, 5423.52; AIC for linear model, 5425.61).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>A U-shaped non-linear association occurred between the type 2 diabetes risk and postoperative weight decrease in gastric cancer survivors who underwent gastrectomy. The lowest type 2 diabetes risk occurred in patients with ≥ −15% to &lt; −10% of postoperative weight decrease at 3 years.</p>\u0000 </section>\u0000 </div>","PeriodicalId":186,"journal":{"name":"Journal of Cachexia, Sarcopenia and Muscle","volume":"14 2","pages":"826-834"},"PeriodicalIF":8.9,"publicationDate":"2023-03-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jcsm.13206","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"6091575","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":"Nicotinamide Phosphoribosyltransferase-elevated NAD+ biosynthesis prevents muscle disuse atrophy by reversing mitochondrial dysfunction","authors":"Yao Zhang,&nbsp;Yingming Wang,&nbsp;Shuai Lu,&nbsp;Rui Zhong,&nbsp;Zhilin Liu,&nbsp;Qichun Zhao,&nbsp;Chongyang Wang","doi":"10.1002/jcsm.13182","DOIUrl":"https://doi.org/10.1002/jcsm.13182","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>It is well known that muscle disuse atrophy is associated with mitochondrial dysfunction, which is implicated in reduced nicotinamide adenine dinucleotide (NAD⁺) levels. Nicotinamide phosphoribosyltransferase (NAMPT), a rate-limiting enzyme in NAD⁺ biosynthesis, may serve as a novel strategy to treat muscle disuse atrophy by reversing mitochondrial dysfunction.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>To investigate the effects of NAMPT on the prevention of disuse atrophy of skeletal muscles predominantly composed of slow-twitch (type I) or fast-twitch (type II) fibres, rabbit models of rotator cuff tear-induced supraspinatus muscle atrophy and anterior cruciate ligament (ACL) transection-induced extensor digitorum longus (EDL) atrophy were established and then administered NAMPT therapy. Muscle mass, fibre cross-sectional area (CSA), fibre type, fatty infiltration, western blot, and mitochondrial function were assayed to analyse the effects and molecular mechanisms of NAMPT in preventing muscle disuse atrophy.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Acute disuse of the supraspinatus muscle exhibited significant loss of mass (8.86 ± 0.25 to 5.10 ± 0.79 g; <i>P</i> &lt; 0.001) and decreased fibre CSA (3939.6 ± 136.1 to 2773.4 ± 217.6 μm², <i>P</i> &lt; 0.001), which were reversed by NAMPT (muscle mass 6.17 ± 0.54 g, <i>P</i> = 0.0033; fibre CSA, 3219.8 ± 289.4 μm², <i>P</i> = 0.0018). Disuse-induced impairment of mitochondrial function were significantly improved by NAMPT, including citrate synthase activity (40.8 ± 6.3 to 50.5 ± 5.6 nmol/min/mg, <i>P</i> = 0.0043), and NAD⁺ biosynthesis (279.9 ± 48.7 to 392.2 ± 43.2 pmol/mg, <i>P</i> = 0.0023). Western blot revealed that NAMPT increases NAD⁺ levels by activating NAMPT-dependent NAD⁺ salvage synthesis pathway. In supraspinatus muscle atrophy due to chronic disuse, a combination of NAMPT injection and repair surgery was more effective than repair in reversing muscle atrophy. Although the predominant composition of EDL muscle is fast-twitch (type II) fibre type that differ from supraspinatus muscle, its mitochondrial function and NAD⁺ levels are also susceptible to disuse. Similar to the supraspinatus muscle, NAMPT-elevated NAD⁺ biosynthesis was also efficient in preventing EDL disuse atrophy by reversing mitochondrial dysfunction.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>NAMPT-elevated NAD⁺ biosynthesis can prevent disuse atrophy of ","PeriodicalId":186,"journal":{"name":"Journal of Cachexia, Sarcopenia and Muscle","volume":"14 2","pages":"1003-1018"},"PeriodicalIF":8.9,"publicationDate":"2023-03-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jcsm.13182","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"5671235","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":"Pilot clinical trial of macimorelin to assess safety and efficacy in patients with cancer cachexia","authors":"Megan Herodes,&nbsp;Lindsey J. Anderson,&nbsp;Samuel Shober,&nbsp;Ellen A. Schur,&nbsp;Solomon A. Graf,&nbsp;Nicola Ammer,&nbsp;Ramiro Salas,&nbsp;Marco Marcelli,&nbsp;Jose M. Garcia","doi":"10.1002/jcsm.13191","DOIUrl":"https://doi.org/10.1002/jcsm.13191","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Cancer cachexia is associated with reduced body weight, appetite and quality of life (QOL) with no approved treatments. Growth hormone secretagogues like macimorelin have potential to mitigate these effects.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>This pilot study assessed the safety and efficacy of macimorelin for 1 week. Efficacy was defined <i>a priori</i> as 1-week change in body weight (≥0.8 kg), plasma insulin-like growth factor (IGF)-1 (≥50 ng/mL) or QOL (≥15%). Secondary outcomes included food intake, appetite, functional performance, energy expenditure and safety laboratory parameters. Patients with cancer cachexia were randomized to 0.5 or 1.0 mg/kg macimorelin or placebo; outcomes were assessed non-parametrically.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Participants receiving at least one of either macimorelin dose were combined (<i>N</i> = 10; 100% male; median age = 65.50 ± 2.12) and compared with placebo (<i>N</i> = 5; 80% male; median age = 68.00 ± 6.19). Efficacy criteria achieved: body weight (macimorelin <i>N</i> = 2; placebo <i>N</i> = 0; <i>P</i> = 0.92); IGF-1 (macimorelin <i>N</i> = 0; placebo <i>N</i> = 0); QOL by Anderson Symptom Assessment Scale (macimorelin <i>N</i> = 4; placebo <i>N</i> = 1; <i>P</i> = 1.00) or Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F; macimorelin <i>N</i> = 3; placebo <i>N</i> = 0; <i>P</i> = 0.50). No related serious or non-serious adverse events were reported. In macimorelin recipients, change in FACIT-F was directly associated with change in body weight (<i>r</i> = 0.92, <i>P</i> = 0.001), IGF-1 (<i>r</i> = 0.80, <i>P</i> = 0.01), and caloric intake (<i>r</i> = 0.83, <i>P</i> = 0.005), and inversely associated with change in energy expenditure (<i>r</i> = −0.67, <i>P</i> = 0.05).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>Daily oral macimorelin for 1 week was safe and numerically improved body weight and QOL in patients with cancer cachexia compared with placebo. Longer term administration should be evaluated for mitigation of cancer-induced reductions in body weight, appetite and QOL in larger studies.</p>\u0000 </section>\u0000 </div>","PeriodicalId":186,"journal":{"name":"Journal of Cachexia, Sarcopenia and Muscle","volume":"14 2","pages":"835-846"},"PeriodicalIF":8.9,"publicationDate":"2023-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jcsm.13191","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"6077113","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":"Impact of osteosarcopenia on disability and mortality among Japanese older adults","authors":"Hiroyuki Shimada,&nbsp;Takao Suzuki,&nbsp;Takehiko Doi,&nbsp;Sangyoon Lee,&nbsp;Sho Nakakubo,&nbsp;Keitaro Makino,&nbsp;Hidenori Arai","doi":"10.1002/jcsm.13209","DOIUrl":"https://doi.org/10.1002/jcsm.13209","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>In clinical settings, muscle mass and bone mineral density assessments are usually performed using dual-energy X-ray absorptiometry (DXA), the clinical standard technique. However, DXA is often unavailable in community settings. This study aimed to determine whether osteoporosis, osteopenia (OP) and sarcopenia (SP) identified by simplified instruments are associated with the future incidence of disability and mortality and evaluate the validity of these instruments as community screening tools. We also examined osteosarcopenia (OS), defined as the coexistence of OP and SP, as a new indicator of geriatric syndromes to determine whether it has an additive effect on adverse outcome incidence compared with OP and SP alone.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>In total, 8995 older adults participated in the study (women: 51.7%, average age: 73.5 ± 5.4 years). Data were extracted from the Japanese national cohort study, National Center for Geriatrics and Gerontology-Study of Geriatric Syndromes. We determined OP based on T-scores generated based on the speed of sound, which is the time taken for ultrasound waves to go through a determined distance in the calcaneus bone. Skeletal muscle mass was evaluated using a bioimpedance analysis device. Handgrip strength and walking speed were measured as physical performance indicators. Incidences of disability and mortality were prospectively determined for 5 years.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>The prevalence of OP, SP and OS was 45.5%, 3.9% and 7.4%, respectively. The incidence of disability in the nonOP/nonSP, OP, SP and OS groups was 6.5%, 14.9%, 20.5% and 33.5%, respectively. The incidence of mortality in the nonOP/nonSP, OP, SP and OS groups was 4.0%, 4.9%, 10.3% and 10.2%, respectively. Participants with OP (hazard ratio [HR]: 1.45, 95% confidence interval [CI]: 1.25–1.68), SP (HR: 1.38, 95% CI: 1.08–1.76) and OS (HR: 1.73, 95% CI: 1.43–2.09) had a higher risk of disability than nonOP/nonSP participants. Participants with OP (HR: 1.31, 95% CI: 1.04–1.64) and OS (HR: 1.45, 95% CI: 1.05–2.00) had a higher risk of mortality than nonOP/nonSP participants. SP was not significantly related to mortality (HR: 1.14, 95% CI: 0.90–1.45). There was no statistical interaction between OP and SP in incident disability and mortality.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>Among older adults, OS identified by bioimpedance and quantitative ultrasound assessments was associated with an increased risk of disability and mortality. Further research is ne","PeriodicalId":186,"journal":{"name":"Journal of Cachexia, Sarcopenia and Muscle","volume":"14 2","pages":"1107-1116"},"PeriodicalIF":8.9,"publicationDate":"2023-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jcsm.13209","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"6044328","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":"Gene polymorphisms associated with heterogeneity and senescence characteristics of sarcopenia in chronic obstructive pulmonary disease","authors":"Amy H. Attaway,&nbsp;Annette Bellar,&nbsp;Nicole Welch,&nbsp;Jinendiran Sekar,&nbsp;Avinash Kumar,&nbsp;Saurabh Mishra,&nbsp;Umur Hatipo?lu,&nbsp;Merry-Lynn McDonald,&nbsp;Elizabeth A. Regan,&nbsp;Jonathan D. Smith,&nbsp;George Washko,&nbsp;Raúl San José Estépar,&nbsp;Peter Bazeley,&nbsp;Joe Zein,&nbsp;Srinivasan Dasarathy","doi":"10.1002/jcsm.13198","DOIUrl":"https://doi.org/10.1002/jcsm.13198","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Sarcopenia, or loss of skeletal muscle mass and decreased contractile strength, contributes to morbidity and mortality in patients with chronic obstructive pulmonary disease (COPD). The severity of sarcopenia in COPD is variable, and there are limited data to explain phenotype heterogeneity. Others have shown that COPD patients with sarcopenia have several hallmarks of cellular senescence, a potential mechanism of primary (age-related) sarcopenia. We tested if genetic contributors explain the variability in sarcopenic phenotype and accelerated senescence in COPD.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>To identify gene variants [single nucleotide polymorphisms (SNPs)] associated with sarcopenia in COPD, we performed a genome-wide association study (GWAS) of fat free mass index (FFMI) in 32 426 non-Hispanic White (NHW) UK Biobank participants with COPD. Several SNPs within the fat mass and obesity-associated (<i>FTO</i>) gene were associated with sarcopenia that were validated in an independent COPDGene cohort (<i>n</i> = 3656). Leucocyte telomere length quantified in the UK Biobank cohort was used as a marker of senescence. Experimental validation was done by genetic depletion of FTO in murine skeletal myotubes exposed to prolonged intermittent hypoxia or chronic hypoxia because hypoxia contributes to sarcopenia in COPD. Molecular biomarkers for senescence were also quantified with FTO depletion in murine myotubes.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Multiple SNPs located in the <i>FTO</i> gene were associated with sarcopenia in addition to novel SNPs both within and in proximity to the gene <i>AC090771.2,</i> which transcribes long non-coding RNA (lncRNA). To replicate our findings, we performed a GWAS of FFMI in NHW subjects from COPDGene. The SNP most significantly associated with FFMI was on chromosome (chr) 16, rs1558902A &gt; T in the <i>FTO</i> gene (β = 0.151, SE = 0.021, <i>P</i> = 1.40 × 10⁻¹² for UK Biobank |β= 0.220, SE = 0.041, <i>P</i> = 9.99 × 10⁻⁸ for COPDGene) and chr 18 SNP rs11664369C &gt; T nearest to the <i>AC090771.2</i> gene (β = 0.129, SE = 0.024, <i>P</i> = 4.64 × 10⁻⁸ for UK Biobank |β = 0.203, SE = 0.045, <i>P</i> = 6.38 × 10⁻⁶ for COPDGene). Lower handgrip strength, a measure of muscle strength, but not FFMI was associated with reduced telomere length in the UK Biobank. Experimentally, in vitro knockdown of <i>FTO</i> lowered myotube diameter and induced a senescence-associated molecular phenotype, which was worsened by prolonged intermittent hypoxia and chronic hypoxia.</p>\u0000 </section>\u0000 \u0000 ","PeriodicalId":186,"journal":{"name":"Journal of Cachexia, Sarcopenia and Muscle","volume":"14 2","pages":"1083-1095"},"PeriodicalIF":8.9,"publicationDate":"2023-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jcsm.13198","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"6044325","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":"Unravelling inclusion body myositis using a patient-derived fibroblast model","authors":"Judith Cantó-Santos,&nbsp;Laura Valls-Roca,&nbsp;Ester Tobías,&nbsp;Francesc Josep García-García,&nbsp;Mariona Guitart-Mampel,&nbsp;Anna Esteve-Codina,&nbsp;Beatriz Martín-Mur,&nbsp;Mercedes Casado,&nbsp;Rafael Artuch,&nbsp;Estel Solsona-Vilarrasa,&nbsp;José Carlos Fernandez-Checa,&nbsp;Carmen García-Ruiz,&nbsp;Carles Rentero,&nbsp;Carlos Enrich,&nbsp;Pedro J. Moreno-Lozano,&nbsp;José César Milisenda,&nbsp;Francesc Cardellach,&nbsp;Josep M. Grau-Junyent,&nbsp;Glòria Garrabou","doi":"10.1002/jcsm.13178","DOIUrl":"https://doi.org/10.1002/jcsm.13178","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Inclusion body myositis (IBM) is an inflammatory myopathy clinically characterized by proximal and distal muscle weakness, with inflammatory infiltrates, rimmed vacuoles and mitochondrial changes in muscle histopathology. There is scarce knowledge on IBM aetiology, and non-established biomarkers or effective treatments are available, partly due to the lack of validated disease models.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>We have performed transcriptomics and functional validation of IBM muscle pathological hallmarks in fibroblasts from IBM patients (<i>n</i> = 14) and healthy controls (<i>n</i> = 12), paired by age and sex. The results comprise an mRNA-seq, together with functional inflammatory, autophagy, mitochondrial and metabolic changes between patients and controls.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Gene expression profile of IBM vs control fibroblasts revealed 778 differentially expressed genes (<i>P</i>-value adj &lt; 0.05) related to inflammation, mitochondria, cell cycle regulation and metabolism. Functionally, an increased inflammatory profile was observed in IBM fibroblasts with higher supernatant cytokine secretion (three-fold increase). Autophagy was reduced considering basal protein mediators (18.4% reduced), time-course autophagosome formation (LC3BII 39% reduced, <i>P</i>-value &lt; 0.05), and autophagosome microscopic evaluation. Mitochondria displayed reduced genetic content (by 33.9%, <i>P</i>-value &lt; 0.05) and function (30.2%-decrease in respiration, 45.6%-decline in enzymatic activity (<i>P</i>-value &lt; 0.001), 14.3%-higher oxidative stress, 135.2%-increased antioxidant defence (<i>P</i>-value &lt; 0.05), 11.6%-reduced mitochondrial membrane potential (<i>P</i>-value &lt; 0.05) and 42.8%-reduced mitochondrial elongation (<i>P</i>-value &lt; 0.05)). In accordance, at the metabolite level, organic acid showed a 1.8-fold change increase, with conserved amino acid profile. Correlating to disease evolution, oxidative stress and inflammation emerge as potential markers of prognosis.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>These findings confirm the presence of molecular disturbances in peripheral tissues from IBM patients and prompt patients' derived fibroblasts as a promising disease model, which may eventually be exported to other neuromuscular disorders. We additionally identify new molecular players in IBM associated with disease progression, setting the path to deepen in disease aetiology, in the identification of novel biomarkers or in the standardizat","PeriodicalId":186,"journal":{"name":"Journal of Cachexia, Sarcopenia and Muscle","volume":"14 2","pages":"964-977"},"PeriodicalIF":8.9,"publicationDate":"2023-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jcsm.13178","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"5654224","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":"Associations between multimorbidity and frailty transitions among older Americans","authors":"Yan Luo,&nbsp;Yuming Chen,&nbsp;Kaipeng Wang,&nbsp;Carson M. De Fries,&nbsp;Ziting Huang,&nbsp;Huiwen Xu,&nbsp;Zhou Yang,&nbsp;Yonghua Hu,&nbsp;Beibei Xu","doi":"10.1002/jcsm.13197","DOIUrl":"https://doi.org/10.1002/jcsm.13197","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>The associations of multimorbidity patterns with transitions between frailty states remain unclear in older individuals.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>We used data from the National Health and Aging Trends Study 2011–2019. Frailty was measured annually using the Fried frailty phenotype. Multimorbidity patterns at baseline were identified using latent class analysis based on 14 chronic conditions. We used the semi-Markov multi-state model to investigate the influences of multimorbidity characterized by condition counts and patterns on subsequent frailty transitions over follow-ups.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Among 9450 participants aged ≥65 years at baseline, 34.8% were non-frail, 48.1% were pre-frail and 17.0% were frail. Over a median follow-up of 4.0 years, 16 880 frailty transitions were observed, with 10 527 worsening and 6353 improving. For 7675 participants with multimorbidity, four multimorbidity patterns were identified: osteoarticular pattern (62.4%), neuropsychiatric–sensory pattern (17.2%), cardiometabolic pattern (10.3%) and complex multimorbidity pattern (10.1%). Compared with no disease, multimorbidity was significantly associated with an increased risk of worsening transitions, including from non-frail to pre-frail (hazard ratio [HR] = 1.35; 95% confidence interval [CI] = 1.21–1.52), from non-frail to frail (HR = 1.68; 95% CI = 1.04–2.73), from pre-frail to frail (HR = 2.19; 95% CI = 1.66–2.90) and from pre-frail to death (HR = 1.64; 95% CI = 1.11–2.41). Compared with the osteoarticular pattern, neuropsychiatric–sensory, cardiometabolic and complex multimorbidity patterns had a significantly higher risk of worsening frailty (all <i>P</i> &lt; 0.05).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>Multimorbidity was associated with dynamic transitions between frailty states and death among older American adults, and the associations varied across multimorbidity patterns. The findings could offer significant implications for public health policymakers in planning interventions and healthcare resources. They also might inform clinicians regarding providing targeted clinical treatment and health management based on multimorbidity patterns of older people.</p>\u0000 </section>\u0000 </div>","PeriodicalId":186,"journal":{"name":"Journal of Cachexia, Sarcopenia and Muscle","volume":"14 2","pages":"1075-1082"},"PeriodicalIF":8.9,"publicationDate":"2023-02-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jcsm.13197","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"5860737","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":"Cellular interplay in skeletal muscle regeneration and wasting: insights from animal models","authors":"Pauline Henrot,&nbsp;Léo Blervaque,&nbsp;Isabelle Dupin,&nbsp;Maéva Zysman,&nbsp;Pauline Esteves,&nbsp;Fares Gouzi,&nbsp;Maurice Hayot,&nbsp;Pascal Pomiès,&nbsp;Patrick Berger","doi":"10.1002/jcsm.13103","DOIUrl":"https://doi.org/10.1002/jcsm.13103","url":null,"abstract":"<p>Skeletal muscle wasting, whether related to physiological ageing, muscle disuse or to an underlying chronic disease, is a key determinant to quality of life and mortality. However, cellular basis responsible for increased catabolism in myocytes often remains unclear. Although myocytes represent the vast majority of skeletal muscle cellular population, they are surrounded by numerous cells with various functions. Animal models, mostly rodents, can help to decipher the mechanisms behind this highly dynamic process, by allowing access to every muscle as well as time-course studies. Satellite cells (SCs) play a crucial role in muscle regeneration, within a niche also composed of fibroblasts and vascular and immune cells. Their proliferation and differentiation is altered in several models of muscle wasting such as cancer, chronic kidney disease or chronic obstructive pulmonary disease (COPD). Fibro-adipogenic progenitor cells are also responsible for functional muscle growth and repair and are associated in disease to muscle fibrosis such as in chronic kidney disease. Other cells have recently proven to have direct myogenic potential, such as pericytes. Outside their role in angiogenesis, endothelial cells and pericytes also participate to healthy muscle homoeostasis by promoting SC pool maintenance (so-called myogenesis–angiogenesis coupling). Their role in chronic diseases muscle wasting has been less studied. Immune cells are pivotal for muscle repair after injury: Macrophages undergo a transition from the M1 to the M2 state along with the transition between the inflammatory and resolutive phase of muscle repair. T regulatory lymphocytes promote and regulate this transition and are also able to activate SC proliferation and differentiation. Neural cells such as terminal Schwann cells, motor neurons and kranocytes are notably implicated in age-related sarcopenia. Last, newly identified cells in skeletal muscle, such as telocytes or interstitial tenocytes could play a role in tissular homoeostasis. We also put a special focus on cellular alterations occurring in COPD, a chronic and highly prevalent respiratory disease mainly linked to tobacco smoke exposure, where muscle wasting is strongly associated with increased mortality, and discuss the pros and cons of animal models versus human studies in this context. Finally, we discuss resident cells metabolism and present future promising leads for research, including the use of muscle organoids.</p>","PeriodicalId":186,"journal":{"name":"Journal of Cachexia, Sarcopenia and Muscle","volume":"14 2","pages":"745-757"},"PeriodicalIF":8.9,"publicationDate":"2023-02-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jcsm.13103","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"5732398","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":"Ten-year longitudinal changes in muscle power, force, and velocity in young, middle-aged, and older adults","authors":"Julian Alcazar,&nbsp;Carlos Rodriguez-Lopez,&nbsp;Christophe Delecluse,&nbsp;Martine Thomis,&nbsp;Evelien Van Roie","doi":"10.1002/jcsm.13184","DOIUrl":"https://doi.org/10.1002/jcsm.13184","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Maximum muscle power (P_max) is a biomarker of physical performance in all ages. No longitudinal studies have assessed the effects of aging on P_max obtained from the torque-velocity (T-V) relationship, which should be considered the ‘gold standard’. This study evaluated the longitudinal changes in the T-V relationship and P_max of the knee-extensor muscles in young, middle-aged, and older adults after 10 years of follow-up.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Four hundred eighty-nine subjects (311 men and 178 women; aged 19–68 years) were tested at baseline and after a 10-year follow-up. Anthropometric data, daily protein intake, physical activity level (PAL), and knee-extension muscle function (isometric, isokinetic, and isotonic) were evaluated. A novel hybrid equation combining a linear and a hyperbolic (Hill-type) region was used to obtain the T-V relationship and P_max of the participants, who were grouped by sex and age (young: 20–40 years; middle-aged: 40–60 years; and old: ≥60 years). Linear mixed-effect models were used to assess effects of time, sex, and age on T-V parameters, P_max, and body mass index (BMI). Additional analyses were performed to adjust for changes in daily protein intake and PAL.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>P_max decreased in young men (−0.6% per year; <i>P</i> &lt; 0.001), middle-aged men and women (−1.1% to −1.4% per year; <i>P</i> &lt; 0.001), and older men and women (−2.2% to −2.4% per year; <i>P</i> ≤ 0.053). These changes were mainly related to decrements in torque at P_max at early age and to decrements in both torque and velocity at P_max at older age. BMI increased among young and middle-aged adults (0.2% to 0.5% per year; <i>P</i> &lt; 0.001), which led to greater declines in relative P_max in those groups. <i>S</i>/T₀, that is, the linear slope of the T-V relationship relative to maximal torque, exhibited a significant decline over time (−0.10%T₀·rad·s⁻¹ per year; <i>P</i> &lt; 0.001), which was significant among middle-aged men and old men and women (all <i>P</i> &lt; 0.05). Annual changes in PAL index were significantly associated to annual changes in P_max (<i>P</i> = 0.017), so the overall decline in P_max was slightly attenuated in the adjusted model (−5.26 vs. −5.05 W per year; both <i>P</i> &lt; 0.001).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>P_max decreased in young, middle","PeriodicalId":186,"journal":{"name":"Journal of Cachexia, Sarcopenia and Muscle","volume":"14 2","pages":"1019-1032"},"PeriodicalIF":8.9,"publicationDate":"2023-02-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jcsm.13184","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"6131879","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}