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     Article first published online:  10 MAR 2017

Elena Conte, Giulia Maria Camerino, Antonietta Mele, Michela De Bellis, Sabata Pierno, Francesco Rana, Adriano Fonzino, Roberta Caloiero, Laura Rizzi, Elena Bresciani, Khoubaib Ben Haj Salah, Jean-Alain Fehrentz, Jean Martinez, Arcangela Giustino, Maria Addolorata Mariggiò, Mauro Coluccia, Domenico Tricarico, Marcello Diego Lograno, Annamaria De Luca, Antonio Torsello, Diana Conte, Antonella Liantonio

Growth hormone secretagogues prevent dysregulation of skeletal muscle calcium homeostasis in a rat model of cisplatin-induced cachexiaBackground
Cachexia is a wasting condition associated with cancer types and, at the same time, is a serious and dose-limiting side effect of cancer chemotherapy. Skeletal muscle loss is one of the main characteristics of cachexia that significantly contributes to the functional muscle impairment. Calcium-dependent signaling pathways are believed to play an important role in skeletal muscle decline observed in cachexia, but whether intracellular calcium homeostasis is affected in this situation remains uncertain. Growth hormone secretagogues (GHS), a family of synthetic agonists of ghrelin receptor (GHS-R1a), are being developed as a therapeutic option for cancer cachexia syndrome; however, the exact mechanism by which GHS interfere with skeletal muscle is not fully understood.
Methods
By a multidisciplinary approach ranging from cytofluorometry and electrophysiology to gene expression and histology, we characterized the calcium homeostasis in fast-twitch extensor digitorum longus (EDL) muscle of adult rats with cisplatin-induced cachexia and established the potential beneficial effects of two GHS (hexarelin and JMV2894) at this level. Additionally, in vivo measures of grip strength and of ultrasonography recordings allowed us to evaluate the functional impact of GHS therapeutic intervention.
Results
Cisplatin-treated EDL muscle fibres were characterized by a ~18% significant reduction of the muscle weight and fibre diameter together with an up-regulation of atrogin1/Murf-1 genes and a down-regulation of Pgc1-a gene, all indexes of muscle atrophy, and by a two-fold increase in resting intracellular calcium, [Ca2+]i, compared with control rats. Moreover, the amplitude of the calcium transient induced by caffeine or depolarizing high potassium solution as well as the store-operated calcium entry were ~50% significantly reduced in cisplatin-treated rats. Calcium homeostasis dysregulation parallels with changes of functional ex vivo (excitability and resting macroscopic conductance) and in vivo (forelimb force and muscle volume) outcomes in cachectic animals. Administration of hexarelin or JMV2894 markedly reduced the cisplatin-induced alteration of calcium homeostasis by both common as well as drug-specific mechanisms of action. This effect correlated with muscle function preservation as well as amelioration of various atrophic indexes, thus supporting the functional impact of GHS activity on calcium homeostasis.
Conclusions
Our findings provide a direct evidence that a dysregulation of calcium homeostasis plays a key role in cisplatin-induced model of cachexia gaining insight into the etiopathogenesis of this form of muscle wasting. Furthermore, our demonstration that GHS administration efficaciously prevents cisplatin-induced calcium homeostasis alteration contributes to elucidate the mechanism of action through which GHS could potentially ameliorate chemotherapy-associated cachexia.

 

Conte, E., Camerino, G. M., Mele, A., De Bellis, M., Pierno, S., Rana, F., Fonzino, A., Caloiero, R., Rizzi, L., Bresciani, E., Ben Haj Salah, K., Fehrentz, J.-A., Martinez, J., Giustino, A., Mariggiò, M. A., Coluccia, M., Tricarico, D., Lograno, M. D., De Luca, A., Torsello, A., Conte, D., and Liantonio, A. (2017) Growth hormone secretagogues prevent dysregulation of skeletal muscle calcium homeostasis in a rat model of cisplatin-induced cachexia. Journal of Cachexia, Sarcopenia and Muscle, doi: 10.1002/jcsm.12185.

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     Article first published online:  1 MAR 2017

Julie Rodriguez, Nicolas Pierre, Damien Naslain, Françoise Bontemps, Daneel Ferreira, Fabian Priem, Louise Deldicque, Marc Francaux

Urolithin B, a newly identified regulator of skeletal muscle massBackground
The control of muscle size is an essential feature of health. Indeed, skeletal muscle atrophy leads to reduced strength, poor quality of life, and metabolic disturbances. Consequently, strategies aiming to attenuate muscle wasting and to promote muscle growth during various (pathological) physiological states like sarcopenia, immobilization, malnutrition, or cachexia are needed to address this extensive health issue. In this study, we tested the effects of urolithin B, an ellagitannin-derived metabolite, on skeletal muscle growth.
Methods
C2C12 myotubes were treated with 15 μM of urolithin B for 24 h. For in vivo experiments, mice were implanted with mini-osmotic pumps delivering continuously 10 μg/day of urolithin B during 28 days. Muscle atrophy was studied in mice with a sciatic nerve denervation receiving urolithin B by the same way.
Results
Our experiments reveal that urolithin B enhances the growth and differentiation of C2C12 myotubes by increasing protein synthesis and repressing the ubiquitin–proteasome pathway. Genetic and pharmacological arguments support an implication of the androgen receptor. Signalling analyses suggest a crosstalk between the androgen receptor and the mTORC1 pathway, possibly via AMPK. In vivo experiments confirm that urolithin B induces muscle hypertrophy in mice and reduces muscle atrophy after the sciatic nerve section.
Conclusions
This study highlights the potential usefulness of urolithin B for the treatment of muscle mass loss associated with various (pathological) physiological states.

 

Rodriguez, J., Pierre, N., Naslain, D., Bontemps, F., Ferreira, D., Priem, F., Deldicque, L., and Francaux, M. (2017) Urolithin B, a newly identified regulator of skeletal muscle mass. Journal of Cachexia, Sarcopenia and Muscle, doi: 10.1002/jcsm.12190.

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     Article first published online:  1 MAR 2017

Marjan Hajahmadi, Sara Shemshadi, Ehsan Khalilipur, Ahmad Amin, Sepideh Taghavi, Majid Maleki, Hadi Malek, Nasim Nader

Muscle wasting in young patients with dilated cardiomyopathyBackground
Muscle wasting can be accelerated by chronic diseases such as heart failure and is one of the major causes of disability, morbidity, and mortality in this population. We aimed to investigate the incidence of muscle wasting and its associated factors in dilated cardiomyopathy patients younger than 55 years of age.
Methods
Between April 2014 and December 2015, all symptomatic patients with a diagnosis of non-ischaemic dilated cardiomyopathy who were referred to heart failure clinic were included in our study.
Dual energy X-ray absorptiometry was used to evaluate body composition and identify muscle wasting. Muscle mass was calculated as the ratio of an individual's total lean mass of legs and arms (also called appendicular skeletal muscle) to their squared height (kg/m2). The muscle mass values of less than 5.45 kg/m2 for women and 7.26 kg/m2 for men were considered low.
Results
A total of 55 patients (32 male) were included. The mean (standard deviation) of age was 37.3 (10.1) years, and the mean of left ventricular ejection fraction was 21.4%. Most of the patients were in the New York Heart Association classes of II and II–III. Twenty-six patients (47.3%) met criteria for muscle wasting. Patients with muscle wasting had lower left ventricular ejection fraction, lower 6-min walk distance, and higher New York Heart Association function class and hospitalization rate.
Conclusions
We concluded that muscle wasting might be present in younger patients with heart failure, particularly in those who are in worse clinical condition.

 

Hajahmadi, M., Shemshadi, S., Khalilipur, E., Amin, A., Taghavi, S., Maleki, M., Malek, H., and Naderi, N. (2017) Muscle wasting in young patients with dilated cardiomyopathy. Journal of Cachexia, Sarcopenia and Muscle, doi: 10.1002/jcsm.12193.

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     Article first published online:  1 MAR 2017

Koji Amano, Isseki Maeda, Tatsuya Morita, Mika Baba, Tomofumi Miura, Takashi Hama, Ichiro Mori, Nobuhisa Nakajima, Tomohiro Nishi, Hiroki Sakurai, Satofumi Shimoyama, Takuya Shinjo, Hiroto Shirayama, Takeshi Yamada, Shigeki Ono, Taketoshi Ozawa, Ryo Yamamoto, Naoki Yamamoto, Hideki Shishido, Hiroya Kinoshita

C-reactive protein, symptoms and activity of daily living in patients with advanced cancer receiving palliative careBackground
The association between C-reactive protein (CRP) level, symptoms, and activities of daily living (ADL) in advanced cancer patients is unclear.
Methods
Secondary data analysis of a multicenter prospective cohort study consisted of 2426 advanced cancer patients referred to palliative care settings was conducted to examine the cross-sectional relationships between CRP level, symptoms, and ADL disabilities. Laboratory data, symptoms, ADL, and manual muscle testing (MMT) results were obtained at baseline. Participants were divided into four groups: low (CRP < 1 mg/dl), moderate (1 = < CRP <5 mg/dl), high (5 = < CRP < 10 mg/dl), and very high CRP (10 mg/dl = < CRP). The proportions of eight symptoms, five ADL disabilities, and three categories of MMT according to the CRP groups were tested by chi-square tests. Multiple-adjusted odd ratios (ORs) were calculated by using ordinal logistic regression after adjustment for age, gender, site of primary cancer, metastatic disease, performance status, chemotherapy, and setting of care.
Results
A total of 1702 patients were analysed. Positive rates of symptoms and ADL disabilities increased with increasing CRP level. In the very high-CRP group, rates of positivity for anorexia, fatigue, and weight loss were 89.8%, 81.0%, and 79.2%, respectively, and over 70% of patients received assistance for bathing, dressing, going to the toilet, and transfer. The grade of MMT also deteriorated with increasing CRP level. Adjusted ORs for the accumulated symptoms significantly increased with increasing CRP level in the moderate-CRP, high-CRP, and very high-CRP groups [1.6 (95% confidence interval 1.2–2.0), P < 0.001; 2.5 (1.9–3.2), P < 0.001; 3.5 (2.7–4.6), P < 0.001, respectively]. Adjusted ORs for the accumulated ADL disabilities significantly increased in the very high-CRP groups [2.1 (1.5–2.9), P < 0.001].
Conclusions
Associations between CRP level, symptoms, and ADL were observed in advanced cancer patients receiving palliative care.

 

Amano, K., Maeda, I., Morita, T., Baba, M., Miura, T., Hama, T., Mori, I., Nakajima, N., Nishi, T., Sakurai, H., Shimoyama, S., Shinjo, T., Shirayama, H., Yamada, T., Ono, S., Ozawa, T., Yamamoto, R., Yamamoto, N., Shishido, H., and Kinoshita, H. (2017) C-reactive protein, symptoms and activity of daily living in patients with advanced cancer receiving palliative care. Journal of Cachexia, Sarcopenia and Muscle, doi: 10.1002/jcsm.12184.

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     Article first published online:  27 FEB 2017

Andrew L. Clark, Andrew J.S. Coats, Henry Krum4, Hugo A. Katus, Paul Mohacsi, Damien Salekin, Melissa K. Schultz, Milton Packer, Stefan D. Anker

Effect of beta-adrenergic blockade with carvedilol on cachexia in severe chronic heart failure: results from the COPERNICUS trialBackground
Cardiac cachexia frequently accompanies the progression of heart failure despite the use of effective therapies for left ventricular dysfunction. Activation of the sympathetic nervous system has been implicated in the pathogenesis of weight loss, but the effects of sympathetic antagonism on cachexia are not well defined.
Methods
We prospectively evaluated changes in body weight in 2289 patients with heart failure who had dyspnoea at rest or on minimal exertion and a left ventricular ejection fraction <25%. Patients were randomly assigned (double-blind) to receive either placebo (n = 1133) or carvedilol (n = 1156) and were followed for the occurrence of major clinical events for up to 29 months (COPERNICUS trial). Patients were not enrolled if they had signs of clinically significant fluid retention due to heart failure.
Results
Patients in the carvedilol group were 33% less likely than patients in the placebo group to experience a further significant loss of weight (>6%) (95% confidence interval: 14–48%, P = 0.002) and were 37% more likely to experience a significant gain in weight (=5%) (95% confidence interval: 12–66%, P = 0.002). Carvedilol's ability to prevent weight loss was most marked in patients with increased body mass index at baseline, whereas its ability to promote weight gain was most marked in patients with decreased body mass index at baseline. Increases in weight were not accompanied by evidence of fluid retention. Baseline values for body mass index and change in body weight were significant predictors of survival regardless of treatment.
Conclusions
Carvedilol attenuated the development and promoted a partial reversal of cachexia in patients with severe chronic heart failure, supporting a role for prolonged sympathetic activation in the genesis of weight loss.

 

Clark, A. L., Coats, A. J. S., Krum, H., Katus, H. A., Mohacsi, P., Salekin, D., Schultz, M. K., Packer, M., and Anker, S. D. (2017) Effect of beta-adrenergic blockade with carvedilol on cachexia in severe chronic heart failure: results from the COPERNICUS trial. Journal of Cachexia, Sarcopenia and Muscle, doi: 10.1002/jcsm.12191.

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     Article first published online:  14 FEB 2017

Elisa Fabbri, Nancy Chiles Shaffer, Marta Gonzalez-Freire, Michelle D. Shardell, Marco Zoli, Stephanie A. Studenski, Luigi Ferrucci

Early body composition, but not body mass, is associated with future accelerated decline in muscle qualityBackground
Muscle quality (MQ) or strength-to-mass ratio declines with aging, but the rate of MQ change with aging is highly heterogeneous across individuals. The identification of risk factors for accelerated MQ decline may offer clues to identity the underpinning physiological mechanisms and indicate targets for prevention and treatment. Using data from the Baltimore Longitudinal Study of Aging, we tested whether measures of body mass and body composition are associated with differential rates of changes in MQ with aging.
Methods
Participants included 511 men and women, aged 50 years or older, followed for an average of 4 years (range: 1–8). MQ was operationalized as ratio between knee-extension isokinetic strength and CT-thigh muscle cross-sectional area. Predictors included body mass and body composition measures: weight (kg), body mass index (BMI, kg/m2), dual-energy x-ray absorptiometry-measured total body fat mass (TFM, kg) and lean mass (TLM, kg), and body fatness (TFM/weight). Covariates were baseline age, sex, race, and body height.
Results
Muscle quality showed a significant linear decline over the time of the follow up (average rate of decline 0.02 Nm/cm2 per year, P < .001). Independent of covariates, neither baseline body weight (P = .756) nor BMI (P = .777) was predictive of longitudinal rate of decline in MQ. Instead, higher TFM and lower TLM at baseline predicted steeper longitudinal decline in MQ (P = .036 and P < .001, respectively). In particular, participants with both high TFM and low TLM at baseline experienced the most dramatic decline compared with those with low TFM and high TLM (about 3% per year vs. 0.5% per year, respectively). Participants in the higher tertile of baseline body fatness presented a significantly faster decline of MQ than the rest of the population (P = .021). Similar results were observed when body mass, TFM, and TLM were modeled as time-dependent predictors.
Conclusions
Body composition, but not weight nor BMI, is associated with future MQ decline, suggesting that preventive strategies aimed at maintaining good MQ with aging should specifically target body composition features.

 

Fabbri, E., Chiles Shaffer, N., Gonzalez-Freire, M., Shardell, M. D., Zoli, M., Studenski, S. A., and Ferrucci, L. (2017) Early body composition, but not body mass, is associated with future accelerated decline in muscle quality. Journal of Cachexia, Sarcopenia and Muscle, doi: 10.1002/jcsm.12183.

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     Article first published online:  2 FEB 2017

Esmee M. Reijnierse, Nynke de Jong, Marijke C. Trappenburg, Gerard Jan Blauw, Gillian Butler-Browne, Helena Gapeyeva, Jean-Yves Hogrel, Jamie S. McPhee, Marco V. Narici, Sarianna Sipilä, Lauri Stenroth, Rob C. van Lummel, Mirjam Pijnappels, Carel G.M. Meskers, Andrea B. Maier

Assessment of maximal handgrip strength: how many attempts are needed?Background
Handgrip strength (HGS) is used to identify individuals with low muscle strength (dynapenia). The influence of the number of attempts on maximal HGS is not yet known and may differ depending on age and health status. This study aimed to assess how many attempts of HGS are required to obtain maximal HGS.
Methods
Three cohorts (939 individuals) differing in age and health status were included. HGS was assessed three times and explored as continuous and dichotomous variable. Paired t-test, intraclass correlation coefficients (ICC) and Bland–Altman analysis were used to test reproducibility of HGS. The number of individuals with misclassified dynapenia at attempts 1 and 2 with respect to attempt 3 were assessed.
Results
Results showed the same pattern in all three cohorts. Maximal HGS at attempts 1 and 2 was higher than at attempt 3 on population level (P < 0.001 for all three cohorts). ICC values between all attempts were above 0.8, indicating moderate to high reproducibility. Bland–Altman analysis showed that 41.0 to 58.9% of individuals had the highest HGS at attempt 2 and 12.4 to 37.2% at attempt 3. The percentage of individuals with a maximal HGS above the gender-specific cut-off value at attempt 3 compared with attempts 1 and 2 ranged from 0 to 50.0%, with a higher percentage of misclassification in middle-aged and older populations.
Conclusions
Maximal HGS is dependent on the number of attempts, independent of age and health status. To assess maximal HGS, at least three attempts are needed if HGS is considered to be a continuous variable. If HGS is considered as a discrete variable to assess dynapenia, two attempts are sufficient to assess dynapenia in younger populations. Misclassification should be taken into account in middle-aged and older populations.

 

Reijnierse, E. M., de Jong, N., Trappenburg, M. C., Blauw, G. J., Butler-Browne, G., Gapeyeva, H., Hogrel, J.-Y., McPhee, J. S., Narici, M. V., Sipilä, S., Stenroth, L., van Lummel, R. C., Pijnappels, M., Meskers, C. G. M., and Maier, A. B. (2017) Assessment of maximal handgrip strength: how many attempts are needed?. Journal of Cachexia, Sarcopenia and Muscle, doi: 10.1002/jcsm.12181.

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     Article first published online:  1 FEB 2017

Serpil Muge Deger, Ping Wang, Rachel Fissell, Charles D. Ellis, Cindy Booker, Feng Sha1, Jennifer L. Morse, Thomas G. Stewart, John C. Gore, Edward D. Siew, Jens Titze, Talat Alp Ikizler

Tissue sodium accumulation and peripheral insulin sensitivity in maintenance hemodialysis patientsBackground
Recent data suggest that sodium (Na+) is stored in the muscle and skin without commensurate water retention in maintenance hemodialysis (MHD) patients. In this study, we hypothesized that excessive Na+ accumulation would be associated with abnormalities in peripheral insulin action.
Methods
Eleven MHD patients and eight controls underwent hyperinsulinemic–euglycemic–euaminoacidemic clamp studies to measure glucose (GDR) and leucine disposal rates (LDR), as well as lower left leg 23Na magnetic resonance imaging to measure Na+ concentration in the muscle and skin tissue.
Results
The median GDR and LDR levels were lower, and the median muscle Na+ concentration was higher in MHD patients compared with controls. No significant difference was found regarding skin Na+ concentration between group comparisons. Linear regression revealed inverse relationships between muscle Na+ concentration and GDR and LDR in MHD patients, whereas no relationship was observed in controls. There was no association between skin Na+ content and GDR or LDR in either MHD patients or controls.
Conclusions
These data suggest that excessive muscle Na+ content might be a determinant of IR in MHD patients, although the causality and mechanisms remain to be proven.

 

Deger, S. M., Wang, P., Fissell, R., Ellis, C. D., Booker, C., Sha, F., Morse, J. L., Stewart, T. G., Gore, J. C., Siew, E. D., Titze, J., and Ikizler, T. A. (2017) Tissue sodium accumulation and peripheral insulin sensitivity in maintenance hemodialysis patients. Journal of Cachexia, Sarcopenia and Muscle, doi: 10.1002/jcsm.12179.

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     Article first published online:  31 JAN 2017

Maria Cristina Gonzalez, Steven B. Heymsfield

Bioelectrical impedance analysis for diagnosing sarcopenia and cachexia: what are we really estimating?As reference methods are not available for identifying low skeletal muscle mass in clinical practice, the European Group on Sarcopenia in Older People the Asian Working Group for Sarcopenia and the International Consensus for Cancer Cachexia guidelines accept bioelectrical impedance analysis (BIA) as an option for sarcopenia and cachexia assessment. Using different BIA equations, several components that represent ‘muscularity’ can be assessed. Total skeletal muscle mass or appendicular skeletal muscle mass normalized in relation to height (skeletal muscle mass index or appendicular skeletal muscle index, respectively) is the most common term used in the consensus. These terms are similar, but they should not be used as synonymous. Both terms can be used to define sarcopenia, but adequate equations and cut-off values should be used according to the studied population. However, there is a disagreement between the sarcopenia definition assessed by using BIA from the European Group on Sarcopenia in Older People and Cachexia Consensus, and this can lead to an overestimation of sarcopenia and, consequently, cachexia. An effort should be made to standardize the terminology employed by the Societies to define low muscularity and sarcopenia by using BIA. Future validation studies may show the need for specific cut-off values for each population using this method.

 

Gonzalez, M. C., and Heymsfield, S. B. (2017) Bioelectrical impedance analysis for diagnosing sarcopenia and cachexia: what are we really estimating?. Journal of Cachexia, Sarcopenia and Muscle, doi: 10.1002/jcsm.12159.

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     Article first published online:  16 JAN 2017

Mariëlle P.K.J. Engelen, V. Suzanne Klimberg, Arianna Allasia, Nicolaas EP Deutz

Presence of early stage cancer does not impair the early protein metabolic response to major surgeryBackground
Combined bilateral mastectomy and reconstruction is a common major surgical procedure in women with breast cancer and in those with a family history of breast cancer. As this large surgical procedure induces muscle protein loss, a preserved anabolic response to nutrition is warranted for optimal recovery. It is unclear whether the presence of early stage cancer negatively affects the protein metabolic response to major surgery as this would mandate perioperative nutritional support.
Methods
In nine women with early stage (Stage II) breast malignancy and nine healthy women with a genetic predisposition to breast cancer undergoing the same large surgical procedure, we examined whether surgery influences the catabolic response to overnight fasting and the anabolic response to nutrition differently. Prior to and within 24?h after combined bilateral mastectomy and reconstruction surgery, whole body protein synthesis and breakdown rates were assessed after overnight fasting and after meal intake by stable isotope methodology to enable the calculation of net protein catabolism in the post-absorptive state and net protein anabolic response to a meal.
Results
Major surgery resulted in an up-regulation of post-absorptive protein synthesis and breakdown rates (P?<?0.001) and lower net protein catabolism (P?<?0.05) and was associated with insulin resistance and increased systemic inflammation (P?<?0.01). Net anabolic response to the meal was reduced after surgery (P?<?0.05) but higher in cancer (P?<?0.05) indicative of a more preserved meal efficiency. The significant relationship between net protein anabolism and the amount of amino acids available in the circulation (R2?=?0.85, P?<?0.001) was independent of the presence of non-cachectic early stage breast cancer or surgery.
Conclusions
The presence of early stage breast cancer does not enhance the normal catabolic response to major surgery or further attenuates the anabolic response to meal intake within 24?h after major surgery in patients with non-cachectic breast cancer. This indicates that the acute anabolic potential to conventional feeding is maintained in non-cachectic early stage breast cancer after major surgery.

 

Engelen, M. P. K. J., Klimberg, V. S., Allasia, A., and Deutz, N. E. (2017) Presence of early stage cancer does not impair the early protein metabolic response to major surgery. Journal of Cachexia, Sarcopenia and Muscle, doi: 10.1002/jcsm.12173.

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     Article first published online:  6 JAN 2017

Ashok Narasimhan, Sunita Ghosh, Cynthia Stretch, Russell Greiner, Oliver F. Bathe, Vickie Baracos, Sambasivarao Damaraju

Small RNAome profiling from human skeletal muscle: novel miRNAs and their targets associated with cancer cachexiaBackground
MicroRNAs (miRs) are small non-coding RNAs that regulate gene (mRNA) expression. Although the pathological role of miRs have been studied in muscle wasting conditions such as myotonic and muscular dystrophy, their roles in cancer cachexia (CC) are still emerging.
Objectives
The objectives are (i) to profile human skeletal muscle expressed miRs; (ii) to identify differentially expressed (DE) miRs between cachectic and non-cachectic cancer patients; (iii) to identify mRNA targets for the DE miRs to gain mechanistic insights; and (iv) to investigate if miRs show potential prognostic and predictive value.
Methods
Study subjects were classified based on the international consensus diagnostic criteria for CC. Forty-two cancer patients were included, of which 22 were cachectic cases and 20 were non-cachectic cancer controls. Total RNA isolated from muscle biopsies were subjected to next-generation sequencing.
Results
A total of 777 miRs were profiled, and 82 miRs with read counts of =5 in 80% of samples were retained for analysis. We identified eight DE miRs (up-regulated, fold change of =1.4 at P?<?0.05). A total of 191 potential mRNA targets were identified for the DE miRs using previously described human skeletal muscle mRNA expression data (n?=?90), and a majority of them were also confirmed in an independent mRNA transcriptome dataset. Ingenuity pathway analysis identified pathways related to myogenesis and inflammation. qRT-PCR analysis of representative miRs showed similar direction of effect (P?<?0.05), as observed in next-generation sequencing. The identified miRs also showed prognostic and predictive value.
Conclusions
In all, we identified eight novel miRs associated with CC.

 

Narasimhan, A., Ghosh, S., Stretch, C., Greiner, R., Bathe, O. F., Baracos, V., and Damaraju, S. (2017) Small RNAome profiling from human skeletal muscle: novel miRNAs and their targets associated with cancer cachexia. Journal of Cachexia, Sarcopenia and Muscle, doi: 10.1002/jcsm.12168.

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     Article first published online:  3 JAN 2017

Jessica M. Scott, David S. Martin, Robert Ploutz-Snyder, Timothy Matz, Timothy Caine, Meghan Downs, Kyle Hackney, Roxanne Buxton, Jeffrey W. Ryder, Lori Ploutz-Snyder

Panoramic ultrasound: a novel and valid tool for monitoring change in muscle massBackground
The strong link between reduced muscle mass and morbidity and mortality highlights the urgent need for simple techniques that can monitor change in skeletal muscle cross-sectional area (CSA). Our objective was to examine the validity of panoramic ultrasound to detect change in quadriceps and gastrocnemius size in comparison with magnetic resonance imaging (MRI) in subjects randomized to 70?days of bed rest (BR) with or without exercise.
Methods
Panoramic ultrasound and MRI images of the quadriceps and gastrocnemius muscles were acquired on the right leg of 27 subjects (26 male, 1 female; age: 34.6?±?7.8?years; body mass: 77.5?±?10.0?kg; body mass index: 24.2?±?2.8?kg/m2; height: 179.1?±?6.9?cm) before (BR-6), during (BR3, 7, 11, 15, 22, 29, 36, 53, 69), and after (BR+3, +6, +10) BR. Validity of panoramic ultrasound to detect change in muscle CSA was assessed by Bland–Altman plots, Lin's concordance correlation coefficient (CCC), sensitivity, specificity, positive predictive value, and negative predictive value.
Results
Six hundred ninety-eight panoramic ultrasound CSA and 698 MRI CSA measurements were assessed. Concordance between ultrasound and MRI was excellent in the quadriceps (CCC: 0.78; P?<?0.0001), whereas there was poor concordance in the gastrocnemius (CCC: 0.37; P?<?0.0006). Compared with MRI, panoramic ultrasound demonstrated high accuracy in detecting quadriceps atrophy and hypertrophy (sensitivity: 73.7%; specificity: 74.2%) and gastrocnemius atrophy (sensitivity: 83.1%) and low accuracy in detecting gastrocnemius hypertrophy (specificity: 33.0%).
Conclusions
Panoramic ultrasound imaging is a valid tool for monitoring quadriceps muscle atrophy and hypertrophy and for detecting gastrocnemius atrophy

 

Scott, J. M., Martin, D. S., Ploutz-Snyder, R., Matz, T., Caine, T., Downs, M., Hackney, K., Buxton, R., Ryder, J. W., and Ploutz-Snyder, L. (2017) Panoramic ultrasound: a novel and valid tool for monitoring change in muscle mass. Journal of Cachexia, Sarcopenia and Muscle, doi: 10.1002/jcsm.12172.

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     Article first published online:  3 JAN 2017

Sorrel T. Burden, Debra J. Gibson, Simon La, James Hill, Mark Pilling, Mattias Soop, Aswatha Ramesh, Chris Todd

Pre-operative oral nutritional supplementation with dietary advice versus dietary advice alone in weight-losing patients with colorectal cancer: single-blind randomized controlled trialBackground
Pre-operative weight loss has been consistently associated with increased post-operative morbidity. The study aims to determine if pre-operative oral nutritional supplements (ONSs) with dietary advice reduce post-operative complications.
Methods
Single-blinded randomized controlled trial. People with colorectal cancer scheduled for surgery with pre-operative weight loss >1?kg/3–6?months were randomized by using stratified blocks (1:1 ratio) in six hospitals (1 November 2013–28 February 2015). Intervention group was given 250?mL/day ONS (10.1?KJ and 0.096?g protein per mL) and dietary advice. Control group received dietary advice alone. Oral nutritional supplements were administered from diagnosis to the day preceding surgery. Research team was masked to group allocation. Primary outcome was patients with one or more surgical site infection (SSI) or chest infection; secondary outcomes included percentage weight loss, total complications, and body composition measurements. Intention-to-treat analysis was performed with both unadjusted and adjusted analyses. A sample size of 88 was required.
Results
Of 101 participants, (55 ONS, 46 controls) 97 had surgery. In intention-to-treat analysis, there were 21/45 (47%) patients with an infection—either an SSI or chest infection in the control group vs. 17/55 (30%) in the ONS group. The odds ratio of a patient incurring either an SSI or chest infection was 0.532 (P?=?0.135 confidence interval 0.232 to 1.218) in the unadjusted analysis and when adjusted for random differences at baseline (age, gender, percentage weight loss, and cancer staging) was 0.341 (P?=?0.031, confidence interval 0.128 to 0.909). Pre-operative percentage weight loss at the first time point after randomization was 4.1% [interquartile range (IQR) 1.7–7.0] in ONS group vs. 6.7% (IQR 2.6–10.8) in controls (Mann–Whitney U P?=?0.021) and post-operatively was 7.4% (IQR 4.3–10.0) in ONS group vs. 10.2% (IQR 5.1–18.5) in controls (P?=?0.016).
Conclusions
Compared with dietary advice alone, ONS resulted in patients having fewer infections and less weight loss following surgery for colorectal cancer. We have demonstrated that pre-operative oral nutritional supplementation can improve clinical outcome in weight losing patients with colorectal cancer.

 


Burden, S. T., Gibson, D. J., Lal, S., Hill, J., Pilling, M., Soop, M., Ramesh, A., and Todd, C. (2017) Pre-operative oral nutritional supplementation with dietary advice versus dietary advice alone in weight-losing patients with colorectal cancer: single-blind randomized controlled trial. Journal of Cachexia, Sarcopenia and Muscle, doi: 10.1002/jcsm.12170.

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     Article first published online:  2 JAN 2017

Merry-Lynn Noelle McDonald, Sungho Won, Manuel Mattheisen, Peter J. Castaldi, Michael H. Cho, Erica Rutten, Megan Hardin, Wai-Ki Yip, Stephen I. Rennard, David A. Lomas, Emiel F.M. Wouters, Alvar Agusti, Richard Casaburi, Christoph P. Lange, George O'Connor, Craig P. Hersh, Edwin K. Silverman

Body mass index change in gastrointestinal cancer and chronic obstructive pulmonary disease is associated with Dedicator of Cytokinesis 1Background
There have been a number of candidate gene association studies of cancer cachexia-related traits, but no genome-wide association study (GWAS) has been published to date. Cachexia presents in patients with a number of complex traits, including both cancer and COPD. The objective of the current investigation was to search for a shared genetic aetiology for change in body mass index (?BMI) among cancer and COPD by using GWAS data in the Framingham Heart Study.
Methods
A linear mixed effects model accounting for age, sex, and change in smoking status was used to calculate ?BMI in participants over 40?years of age with three consecutive BMI time points (n?=?4162). Four GWAS of ?BMI using generalized estimating equations were performed among 1085 participants with a cancer diagnosis, 204 with gastrointestinal (GI) cancer, 112 with lung cancer, and 237 with COPD to test for association with 418?365 single-nucleotide polymorphisms (SNPs).
Results
Two SNPs reached a level of genome-wide significance (P?<?5?×?10-8) with ?BMI: (i) rs41526344 within the CNTN4 gene, among COPD cases (ß?=?0.13, P?=?4.3?×?10-8); and (ii) rs4751240 in the gene Dedicator of Cytokinesis 1 (DOCK1) among GI cancer cases (ß?=?0.10, P?=?1.9?×?10-8). The DOCK1 SNP association replicated in the ?BMI GWAS among COPD cases (ßmeta-analyis?=?0.10, Pmeta-analyis?=?9.3?×?10-10). The DOCK1 gene codes for the dedicator of cytokinesis 1 protein, which has a role in myoblast fusion.
Conclusions
In sum, one statistically significant common variant in the DOCK1 gene was associated with ?BMI in GI cancer and COPD cases providing support for at least partially shared aetiology of ?BMI in complex diseases.

 


McDonald, M.-L. N., Won, S., Mattheisen, M., Castaldi, P. J., Cho, M. H., Rutten, E., Hardin, M., Yip, W. -K., Rennard, S. I., Lomas, D. A., Wouters, E. F. M., Agusti, A., Casaburi, R., Lange, C. P., O'Connor, G., Hersh, C. P., and Silverman, E. K. (2017) Body mass index change in gastrointestinal cancer and chronic obstructive pulmonary disease is associated with Dedicator of Cytokinesis 1. Journal of Cachexia, Sarcopenia and Muscle, doi: 10.1002/jcsm.12171.

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     Article first published online:  26 DEC 2016

Julie A. Pasco, Mohammadreza Mohebbi, Kara L. Holloway, Sharon L. Brennan-Olsen, Natalie K. Hyde, Mark A. Kotowicz

Musculoskeletal decline and mortality: prospective data from the Geelong Osteoporosis StudyBackground
We aimed to examine the relationship between musculoskeletal deterioration and all-cause mortality in a cohort of women studied prospectively over a decade.
Methods
A cohort of 750 women aged 50–94?years was followed for a decade after femoral neck bone mineral density (BMD) and appendicular lean mass (ALM) were measured using dual energy X-ray absorptiometry, in conjunction with comorbidities, health behaviour data, and other clinical measures. The outcome was all-cause mortality identified from the Australian National Deaths Index. Using Cox proportional hazards models and age as the time variable, mortality risks were estimated according to BMD groups (ideal-BMD, osteopenia, and osteoporosis) and ALM groups (T-scores?>?-1.0 high, -2.0 to -1.0 medium, <-2.0 low).
Results
During 6712 person years of follow-up, there were 190 deaths, the proportions increasing with diminishing BMD: 10.7% (23/215) ideal-BMD, 23.5% (89/378) osteopenia, 49.7% (78/157) osteoporosis; and with diminishing ALM: 17.0% (59/345) high, 26.2% (79/301) medium, 50.0% (52/104) low. In multivariable models adjusted for smoking, polypharmacy, and mobility, compared with those with ideal BMD, mortality risk was greater for those with osteopenia [hazard ratio (HR) 1.77, 95% confidence interval (CI) 1.11–2.81] and osteoporosis (HR 2.61, 95%CI 1.60–4.24). Similarly, compared with those with high ALM, adjusted mortality risk was greater for medium ALM (HR 1.36, 95%CI 0.97–1.91) and low ALM (HR 1.65, 95%CI 1.11–2.45). When BMD and ALM groups were tested together in the model, BMD remained a predictor of mortality (HR 1.74, 95%CI 1.09–2.78; HR 2.82, 95%CI 1.70–4.70; respectively), and low ALM had borderline significance (HR 1.52, 95%CI 1.00–2.31), which was further attenuated after adjusting for smoking, polypharmacy, and mobility.
Conclusions
Poor musculoskeletal health increased the risk for mortality independent of age. This appears to be driven mainly by a decline in bone mass. Low lean mass independently exacerbated mortality risk, and this appeared to operate through poor health exposures.

 

Pasco, J. A., Mohebbi, M., Holloway, K. L., Brennan-Olsen, S. L., Hyde, N. K., and Kotowicz, M. A. (2016) Musculoskeletal decline and mortality: prospective data from the Geelong Osteoporosis Study. Journal of Cachexia, Sarcopenia and Muscle, doi: 10.1002/jcsm.12177.

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     Article first published online:  29 NOV 2016

Aiko Inoue, Xian Wu Cheng, Zhe Huang, Lina Hu, Ryosuke Kikuchi, Haiying Jiang, Limei Piao, Takeshi Sasaki, Kohji Itakura, Hongxian Wu, Guangxian Zhao, Yanna Lei, Guang Yang, Enbo Zhu, Xiang Li, Kohji Sato, Teruhiko Koike, Masafumi Kuzuya

Exercise restores muscle stem cell mobilization, regenerative capacity and muscle metabolic alterations via adiponectin/AdipoR1 activation in SAMP10 miceBackground
Exercise train (ET) stimulates muscle response in pathological conditions, including aging. The molecular mechanisms by which exercise improves impaired adiponectin/adiponectin receptor 1 (AdipoR1)-related muscle actions associated with aging are poorly understood. Here we observed that in a senescence-accelerated mouse prone 10 (SAMP10) model, long-term ET modulated muscle-regenerative actions.
Methods
25-week-old male SAMP10 mice were randomly assigned to the control and the ET (45 min/time, 3/week) groups for 4 months. Mice that were maintained in a sedentary condition served controls.
Results
ET ameliorated aging-related muscle changes in microstructure, mitochondria, and performance. The amounts of proteins or mRNAs for p-AMPKα, p-Akt, p-ERK1/2, p-mTOR, Bcl-XL, p-FoxO3, peroxisome proliferators-activated receptor-γ coactivator, adiponectin receptor1 (adpoR1), and cytochrome c oxidase-IV, and the numbers of CD34+/integrin-α7+ muscle stem cells (MuSCs) and proliferating cells in the muscles and bone-marrow were enhanced by ET, whereas the levels of p-GSK-3α and gp91phox proteins and apoptotic cells were reduced by ET. The ET also resulted in increased levels of plasma adiponectin and the numbers of bone-marrow (BM)-derived circulating CD34+/integrin-α7+ MuSCs and their functions. Integrin-α7+ MuSCs of exercised mice had improved changes of those beneficial molecules. These ET-mediated aged muscle benefits were diminished by adiponectin and AdipoR1 blocking as well as AMPK inhibition. Finally, recombinant mouse adiponectin enhanced AMPK and mTOR phosphorylations in BM-derived integrin-α7+ cells.
Conclusions
These findings suggest that ET can improve aging-related impairments of BM-derived MuSC regenerative capacity and muscle metabolic alterations via an AMPK-dependent mechanism that is mediated by an adiponectin/AdipoR1 axis in SAMP10 mice.

 


Inoue, A., Cheng, X. W., Huang, Z., Hu, L., Kikuchi, R., Jiang, H., Piao, L., Sasaki, T., Itakura, K., Wu, H., Zhao, G., Lei, Y., Yang, G., Zhu, E., Li, X., Sato, K., Koike, T., and Kuzuya, M. (2016) Exercise restores muscle stem cell mobilization, regenerative capacity and muscle metabolic alterations via adiponectin/AdipoR1 activation in SAMP10 mice. Journal of Cachexia, Sarcopenia and Muscle, doi: 10.1002/jcsm.12166.

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     Article first published online:  28 NOV 2016

Oliver Klassen, Martina E. Schmidt, Cornelia M. Ulrich, Andreas Schneeweiss, Karin Potthoff, Karen Steindorf, Joachim Wiskemann

Muscle strength in breast cancer patients receiving different treatment regimesBackground
Muscle dysfunction and sarcopenia have been associated with poor performance status, an increased mortality risk, and greater side effects in oncologic patients. However, little is known about how performance is affected by cancer therapy. We investigated muscle strength in breast cancer patients in different adjuvant treatment settings and also compared it with data from healthy individuals.
Methods
Breast cancer patients (N = 255) from two randomized controlled exercise trials, staged 0–III and aged 54.4 ± 9.4 years, were categorized into four groups according to their treatment status. In a cross-sectional design, muscle function was assessed bilaterally by isokinetic dynamometry (0°, 60°, 180°/s) as maximal voluntary isometric contraction (MVIC) and maximal isokinetic peak torque (MIPT) in shoulder rotators and knee flexors and extensors. Additionally, muscular fatigue index (FI%) and shoulder flexibility were evaluated. Healthy women (N = 26), aged 53.3 ± 9.8 years, were tested using the same method. Analysis of covariance was used to estimate the impact of different cancer treatments on skeletal muscle function with adjustment for various clinical and socio-demographic factors.
Results
Consistently, lower muscle strength was measured in shoulder and knee strength in patients after chemotherapy. On average, patients had up to 25% lower strength in lower extremities and 12–16% in upper extremities in MVIC and MIPT during cancer treatment compared with healthy women. No substantial difference between patient groups in shoulder strength, but significantly lower shoulder flexibility in patients with radical mastectomy was measured. Chemotherapy-treated patients had consistently higher FI%. No serious adverse events were reported.
Conclusions
Breast cancer patients showed markedly impaired muscle strength and joint dysfunctions before and after anticancer treatment. The significant differences between patients and healthy individuals underline the need of exercise therapy as early as possible in order to prevent or counteract the loss of muscle function after curative surgery as well as the consequences of neo-/adjuvant chemotherapy.


Yang, M., Hu, X., Wang, H., Zhang, L., Hao, Q., and Dong, B. (2016) Sarcopenia predicts readmission and mortality in elderly patients in acute care wards: a prospective study. Journal of Cachexia, Sarcopenia and Muscle, doi: 10.1002/jcsm.12163.

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     Article first published online:  28 NOV 2016

Ming Yang, Xiaoyi Hu, Haozhong Wang, Lei Zhang, Qiukui Hao, Birong Dong

Sarcopenia predicts readmission and mortality in elderly patients in acute care wards: a prospective studyObjectives
The aim of this study is to assess the prevalence of sarcopenia and investigate the associations between sarcopenia and long-term mortality and readmission in a population of elderly inpatients in acute care wards.
Methods
We conducted a prospective observational study in the acute care wards of a teaching hospital in western China. The muscle mass was estimated according to a previously validated anthropometric equation. Handgrip strength was measured with a handheld dynamometer, and physical performance was measured via a 4 m walking test. Sarcopenia was defined according to the recommended diagnostic algorithm of the Asia Working Group for Sarcopenia. The survival status and readmission information were obtained via telephone interviews at 12, 24, and 36 months during the 3 year follow-up period following the baseline investigation.
Results
Two hundred and eighty-eight participants (mean age: 81.1 ± 6.6 years) were included. Forty-nine participants (17.0%) were identified as having sarcopenia. This condition was similar in men and women (16.9% vs. 17.5%, respectively, P = 0.915). During the 3 year follow-up period, 49 men (22.7%) and 9 women (16.4%) died (P = 0.307). The mortality of sarcopenic participants was significantly increased compared with non-sarcopenic participants (40.8% vs. 17.1%, respectively, P < 0.001). After adjusting for age, sex and other confounders, sarcopenia was an independent predictor of 3 year mortality (adjusted hazard ratio: 2.49; 95% confidential interval: 1.25–4.95) and readmission (adjusted hazard ratio: 1.81; 95% confidential interval: 1.17–2.80).
Conclusions
Sarcopenia, which is evaluated by a combination of anthropometric measures, gait speed, and handgrip strength, is valuable to predict hospital readmission and long-term mortality in elderly patients in acute care wards.


Yang, M., Hu, X., Wang, H., Zhang, L., Hao, Q., and Dong, B. (2016) Sarcopenia predicts readmission and mortality in elderly patients in acute care wards: a prospective study. Journal of Cachexia, Sarcopenia and Muscle, doi: 10.1002/jcsm.12163.

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     Article first published online:  22 NOV 2016

Jeroen L.A. van Vugt, Stef Levolger, Arvind Gharbharan, Marcel Koek, Wiro J. Niessen, Jacobus W.A. Burger, Sten P. Willemsen, Ron W.F. de Bruin, Jan N.M. IJzermans

A comparative study of software programmes for cross-sectional skeletal muscle and adipose tissue measurements on abdominal computed tomography scans of rectal cancer patientsBackground
The association between body composition (e.g. sarcopenia or visceral obesity) and treatment outcomes, such as survival, using single-slice computed tomography (CT)-based measurements has recently been studied in various patient groups. These studies have been conducted with different software programmes, each with their specific characteristics, of which the inter-observer, intra-observer, and inter-software correlation are unknown. Therefore, a comparative study was performed.
Methods
Fifty abdominal CT scans were randomly selected from 50 different patients and independently assessed by two observers. Cross-sectional muscle area (CSMA, i.e. rectus abdominis, oblique and transverse abdominal muscles, paraspinal muscles, and the psoas muscle), visceral adipose tissue area (VAT), and subcutaneous adipose tissue area (SAT) were segmented by using standard Hounsfield unit ranges and computed for regions of interest. The inter-software, intra-observer, and inter-observer agreement for CSMA, VAT, and SAT measurements using FatSeg, OsiriX, ImageJ, and sliceOmatic were calculated using intra-class correlation coefficients (ICCs) and Bland–Altman analyses. Cohen's κ was calculated for the agreement of sarcopenia and visceral obesity assessment. The Jaccard similarity coefficient was used to compare the similarity and diversity of measurements.
Results
Bland–Altman analyses and ICC indicated that the CSMA, VAT, and SAT measurements between the different software programmes were highly comparable (ICC 0.979–1.000, P < 0.001). All programmes adequately distinguished between the presence or absence of sarcopenia (κ = 0.88–0.96 for one observer and all κ = 1.00 for all comparisons of the other observer) and visceral obesity (all κ = 1.00). Furthermore, excellent intra-observer (ICC 0.999–1.000, P < 0.001) and inter-observer (ICC 0.998–0.999, P < 0.001) agreement for all software programmes were found. Accordingly, excellent Jaccard similarity coefficients were found for all comparisons (mean ≥ 0.964).
Conclusions
FatSeg, OsiriX, ImageJ, and sliceOmatic showed an excellent agreement for CSMA, VAT, and SAT measurements on abdominal CT scans. Furthermore, excellent inter-observer and intra-observer agreement were achieved. Therefore, results of studies using these different software programmes can reliably be compared.

 


van Vugt, J. L. A., Levolger, S., Gharbharan, A., Koek, M., Niessen, W. J., Burger, J. W. A., Willemsen, S. P., de Bruin, R. W. F., and IJzermans, J. N. M. (2016) A comparative study of software programmes for cross-sectional skeletal muscle and adipose tissue measurements on abdominal computed tomography scans of rectal cancer patients. Journal of Cachexia, Sarcopenia and Muscle, doi: 10.1002/jcsm.12158.

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     Article first published online:  21 NOV 2016

Michael P. Chu, Jessica Lieffers, Sunita Ghosh, Andrew Belch, Neil S. Chua, Amelie Fontaine, Randeep Sangha, Robert A. Turner, Vickie E. Baracos andMichael B. Sawyer

Skeletal muscle density is an independent predictor of diffuse large B-cell lymphoma outcomes treated with rituximab-based chemoimmunotherapyBackground
While much cancer research focuses on tumours and their microenvironment, malignancies cause widespread physiologic changes. Cancer and treatment-related sarcopenia, measured with quantitative imaging or as a decrease in overall body mass, are indicative of poor prognosis in elderly diffuse large B-cell lymphoma (DLBCL) patients, skeletal muscle radiodensity (SMD) may be a better prognostic marker. SMD, a measure of muscle radiation attenuation on CT imaging, is more prognostic than sarcopenia or International Prognostic Index (IPI) scores in follicular lymphoma and multiple solid organ malignancies. Low SMD appears to correlate with fat accumulation in muscle and is associated with inflammation. This study set out to examine SMD's prognostic ability in DLBCL.
Methods
All DLBCL patients treated with rituximab-containing therapy between 2004 and 2009 were compared to determine SMD's prognostic ability in this single centre, retrospective study. Pre-treatment CT scans were used to measure SMD and muscle cross-sectional area. Primary endpoints included progression free (PFS) and overall survival (OS) while objective response rates (ORR) were secondary.
Results
Of 224 evaluable patients, 116 were identified as having low SMD. Low SMD predicted poorer 5 year PFS, 60 vs. 81% (p = 0.001) and OS, 58 vs. 86% (p < 0.0001). SMD's prognostic ability retained significance in multivariate analysis taking into consideration the Revised International Prognostic Index (R-IPI) and sex. Although high SMD was not predictive of ORR (95.4 vs. 91.4%, p = 0.17), it was strongly associated with radiographic complete response (85 vs. 66%, p = 0.0007). Contrary to previous findings, sarcopenia did not predict for poorer OS but suggested improved OS in elderly DLBCL patients (HR 0.38, p = 0.01).
Conclusions
SMD is a novel prognostic (and potentially treatment predictive) marker independent of R-IPI in DLBCL. It presents an inexpensive yet complementary assessment to R-IPI for prognosticating DLBCL outcomes.

 


Chu, M. P., Lieffers, J., Ghosh, S., Belch, A., Chua, N. S., Fontaine, A., Sangha, R., Turner, R. A., Baracos, V. E., and Sawyer, M. B. (2016) Skeletal muscle density is an independent predictor of diffuse large B-cell lymphoma outcomes treated with rituximab-based chemoimmunotherapy. Journal of Cachexia, Sarcopenia and Muscle, doi: 10.1002/jcsm.12161.

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     Article first published online:  17 NOV 2016

Rizhen Yu, Ji-an Chen, Jing Xu, Jin Cao, Yanlin Wang, Sandhya S. Thomas, Zhaoyong Hu

Suppression of muscle wasting by the plant-derived compound ursolic acid in a model of chronic kidney diseaseBackground
Muscle wasting in chronic kidney disease (CKD) and other catabolic disorders contributes to morbidity and mortality, and there are no therapeutic interventions that regularly and safely block losses of muscle mass. We have obtained evidence that impaired IGF-1/insulin signalling and increases in glucocorticoids, myostatin and/or inflammatory cytokines that contribute to the development of muscle wasting in catabolic disorders by activating protein degradation.
Methods
Using in vitro and in vivo models of muscle wasting associated with CKD or dexamethasone administration, we measured protein synthesis and degradation and examined mechanisms by which ursolic acid, derived from plants, could block the loss of muscle mass stimulated by CKD or excessive levels of dexamethasone.
Results
Using cultured C2C12 myotubes to study muscle wasting, we found that exposure to glucocorticoids cause loss of cell proteins plus an increase in myostatin; both responses are significantly suppressed by ursolic acid. Results from promoter and ChIP assays demonstrated a mechanism involving ursolic acid blockade of myostatin promoter activity that is related to CEBP/δ expression. In mouse models of CKD-induced or dexamethasone-induced muscle wasting, we found that ursolic acid blocked the loss of muscle mass by stimulating protein synthesis and decreasing protein degradation. These beneficial responses included decreased expression of myostatin and inflammatory cytokines (e.g. TGF-β, IL-6 and TNFα), which are initiators of muscle-specific ubiquitin-E3 ligases (e.g. Atrogin-1, MuRF-1 and MUSA1).
Conclusions
Ursolic acid improves CKD-induced muscle mass by suppressing the expression of myostatin and inflammatory cytokines via increasing protein synthesis and reducing proteolysis.

 

Yu, R., Chen, J., Xu, J., Cao, J., Wang, Y., Thomas, S. S., and Hu, Z. (2016) Suppression of muscle wasting by the plant-derived compound ursolic acid in a model of chronic kidney disease. Journal of Cachexia, Sarcopenia and Muscle, doi: 10.1002/jcsm.12162.

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     Article first published online:  16 NOV 2016

Richard Matthew Dodds, Antoneta Granic, Karen Davies, Thomas B. L. Kirkwood, Carol Jagger, Avan Aihie Sayer

Prevalence and incidence of sarcopenia in the very old: findings from the Newcastle 85+ StudyIntroduction
Recognition that an older person has sarcopenia is important because this condition is linked to a range of adverse outcomes. Sarcopenia becomes increasingly common with age, and yet there are few data concerning its descriptive epidemiology in the very old (aged 85 years and above). Our aims were to describe risk factors for sarcopenia and estimate its prevalence and incidence in a British sample of the very old.
Methods
We used data from two waves (2006/07 and 2009/10) of the Newcastle 85+ Study, a cohort born in 1921 and registered with a Newcastle/North Tyneside general practice. We assessed sarcopenia status using the European Working Group on Sarcopenia in Older People (EWGSOP) definition. Grip strength was measured using a Takei digital dynamometer (Takei Scientific Instruments Ltd., Niigata, Japan), gait speed was calculated from the Timed Up and Go test, and lean mass was estimated using a Tanita-305 body fat analyzer. We used logistic regression to examine associations between risk factors for prevalent sarcopenia at baseline and incident sarcopenia at follow-up.
Results
European Working Group on Sarcopenia in Older People sarcopenia was present in 21% of participants at baseline [149/719 participants, mean age 85.5 (0.4) years]. Many participants had either slow gait speed or weak grip strength (74.3%), and hence measurement of muscle mass was frequently indicated by the EWGSOP definition. Incidence data were available for 302 participants, and the incident rate was 3.7 cases per 100 person years at risk. Low Standardized Mini-Mental State Examination, lower occupational social class, and shorter duration of education were associated with sarcopenia at baseline, while low muscle mass was associated with incident sarcopenia. Low body mass index (BMI) was a risk factor for both in a graded fashion, with each unit decrease associated with increased odds of prevalent [odds ratio (OR) 1.29, 95% confidence interval (CI): 1.21, 1.37] and incident (OR 1.20, 95% CI: 1.08, 1.33) sarcopenia.
Conclusions
To our knowledge, this is the first study to describe prevalence and incidence of EWGSOP sarcopenia in the very old. Low BMI was a risk factor for both current and future sarcopenia; indeed, there was some evidence that low BMI may be a reasonable proxy for low lean mass. Overall, the high prevalence of sarcopenia among the very old suggests that this group should be a focus for future research.

 

Dodds, R. M., Granic, A., Davies, K., Kirkwood, T. B. L., Jagger, C., and Sayer, A. A. (2016) Prevalence and incidence of sarcopenia in the very old: findings from the Newcastle 85+ Study. Journal of Cachexia, Sarcopenia and Muscle, doi: 10.1002/jcsm.12157.

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     Article first published online:  8 NOV 2016

Leandro dos Santos, Edilson S. Cyrino, Melissa Antunes, Diana A. Santos, Luís B. Sardinha

Sarcopenia and physical independence in older adults: the independent and synergic role of muscle mass and muscle functionBackground
The loss of skeletal muscle mass (MM) or muscle function (MF) alone increases the risk for losing physical independence in older adults. We aimed to examine the independent and synergic associations of low MM and low MF, both criteria of sarcopenia, with the risk for losing projected physical independence in later life (+90?years old).
Methods
Cross-sectional analyses were conducted in 3493 non-institutionalized older adults (1166 males). Physical independence was assessed with a 12-item composite physical function scale. Logistic regression was used to estimate the odds-ratio (OR) for being at risk for losing physical independence.
Results
Approximately 30% of the participants were at risk for losing physical independence at 90?years of age. Independent analysis demonstrated that participants with low MM had 1.65 (95%CI: 1.27–2.31) increased odds for being at risk for losing physical independence and participants with low MF had 6.19 (95%CI 5.08–7.53) increased odds for being at risk. Jointly, having a low MM and a low MF increased the risk for losing physical independence to 12.28 (95%CI 7.95 to 18.96).
Conclusions
Although low MM represents a risk factor for losing physical independence, low MF seems to play a more dominant role in this relationship, with the presence of both sarcopenia criteria representing a substantial risk for losing physical independence in later life.

 

dos Santos, L., Cyrino, E. S., Antunes, M., Santos, D. A., and Sardinha, L. B. (2016) Sarcopenia and physical independence in older adults: the independent and synergic role of muscle mass and muscle function. Journal of Cachexia, Sarcopenia and Muscle, doi: 10.1002/jcsm.12160.

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     Article first published online:  26 OCT 2016

David P. J. van Dijk, Maikel J. A. M. Bakens, Mariëlle M. E. Coolsen, Sander S. Rensen, Ronald M. van Dam, Martijn J. L. Bours, Matty P. Weijenberg, Cornelis H. C. Dejong, Steven W. M. Olde Damink

Low skeletal muscle radiation attenuation and visceral adiposity are associated with overall survival and surgical site infections in patients with pancreatic cancerBackground
Cancer cachexia and skeletal muscle wasting are related to poor survival. In this study, quantitative body composition measurements using computed tomography (CT) were investigated in relation to survival, post-operative complications, and surgical site infections in surgical patients with cancer of the head of the pancreas.
Methods
A prospective cohort of 199 patients with cancer of the head of the pancreas was analysed by CT imaging at the L3 level to determine (i) muscle radiation attenuation (average Hounsfield units of total L3 skeletal muscle); (ii) visceral adipose tissue area; (iii) subcutaneous adipose tissue area; (iv) intermuscular adipose tissue area; and (v) skeletal muscle area. Sex-specific cut-offs were determined at the lower tertile for muscle radiation attenuation and skeletal muscle area and the higher tertile for adipose tissues. These variables of body composition were related to overall survival, severe post-operative complications (Dindo–Clavien ≥ 3), and surgical site infections (wounds inspected daily by an independent trial nurse) using Cox-regression analysis and multivariable logistic regression analysis, respectively.
Results
Low muscle radiation attenuation was associated with shorter survival in comparison with moderate and high muscle radiation attenuation [median survival 10.8 (95% CI: 8.8–12.8) vs. 17.4 (95% CI: 14.7–20.1), and 18.5 (95% CI: 9.2–27.8) months, respectively; P < 0.008]. Patient subgroups with high muscle radiation attenuation combined with either low visceral adipose tissue or age <70 years had longer survival than other subgroups (P = 0.011 and P = 0.001, respectively). Muscle radiation attenuation was inversely correlated with intermuscular adipose tissue (rp = −0.697, P < 0.001). High visceral adipose tissue was associated with an increased surgical site infection rate, OR: 2.4 (95% CI: 1.1–5.3; P = 0.027).
Conclusions
Low muscle radiation attenuation was associated with reduced survival, and high visceral adiposity was associated with an increase in surgical site infections. The strong correlation between muscle radiation attenuation and intermuscular adipose tissue suggests the presence of ectopic fat in muscle, warranting further investigation. CT image analysis could be implemented in pre-operative risk assessment to assist in treatment decision-making.

 

 

van Dijk, D. P. J., Bakens, M. J. A. M., Coolsen, M. M. E., Rensen, S. S., van Dam, R. M., Bours, M. J. L., Weijenberg, M. P., Dejong, C. H. C.,  Olde Damink, S. W. M. (2016) Low skeletal muscle radiation attenuation and visceral adiposity are associated with overall survival and surgical site infections in patients with pancreatic cancer. Journal of Cachexia, Sarcopenia and Muscle, doi: 10.1002/jcsm.12155.

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     Article first published online:  22 OCT 2016

Charlotte Beaudart, Emmanuel Biver, Jean-Yves Reginster, René Rizzoli, Yves Rolland, Ivan Bautmans, Jean Petermans, Sophie Gillain, Fanny Buckinx, Nadia Dardenne, Olivier Bruyère

Validation of the SarQoL®, a specific health-related quality of life questionnaire for SarcopeniaBackground
A specific self-administrated health-related quality of life questionnaire for sarcopenia, the Sarcopenia and Quality Of Life (SarQoL®), has been recently developed. This questionnaire is composed of 55 items translated into 22 questions and organized into seven domains of quality of life. The objective of the present work is to evaluate the psychometric properties (discriminative power, validity, reliability, floor and ceiling effects) of the SarQoL® questionnaire.
Methods
Sarcopenic subjects were recruited in an outpatient clinic in Liège, Belgium and were diagnosed according to the algorithm developed by the European Working Group on Sarcopenia in Older People. We compared the score of the SarQoL® between sarcopenic and non-sarcopenic subjects using a logistic regression after adjustment for potential confounding variables. Internal consistency reliability was determined using Cronbach's alpha coefficient; construct validity was assessed using convergent and divergent validities. Test–retest reliability was verified after a two-week interval using the intra-class correlation coefficient (ICC). At last, floor and ceiling effects were also tested.
Results
A total of 296 subjects with a median age of 73.3 (68.9–78.6) years were recruited for this study. Among them, 43 were diagnosed sarcopenic. After adjustment for potential confounding factors, the total score and the scores of the different dimensions of the SarQoL® questionnaire were significantly lower for sarcopenic than for non-sarcopenic subjects (54.7 (45.9–66.3) for sarcopenic vs. 67.8 (57.3 – 79.0) for non sarcopenic, OR 0.93 (95%CI 0.90–0.96)). Regarding internal consistency, the Cronbach's alpha coefficient was 0.87. The SarQoL® questionnaire data showed good correlation with some domains of the Short-Form 36 (SF-36) and the EuroQoL 5-dimension (EQ-5D) questionnaires and with the mobility test. An excellent agreement between the test and the retest was found with an ICC of 0.91 (95% CI 0.82–0.95). At last, neither floor nor ceiling effects were detected.
Conclusions
The SarQoL® questionnaire is valid, consistent, and reliable and can therefore be recommended for clinical and research purposes. However, its sensitivity to change needs to be assessed in future longitudinal studies.

 

Beaudart, C., Biver, E., Reginster, J. -Y., Rizzoli, R., Rolland, Y., Bautmans, I., Petermans, J., Gillain, S., Buckinx, F., Dardenne, N.,  Bruyère, O. (2016) Validation of the SarQoL®, a specific health-related quality of life questionnaire for Sarcopenia. Journal of Cachexia, Sarcopenia and Muscle, doi: 10.1002/jcsm.12149.

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     Article first published online:  10 OCT 2016

Sheng-Chih Huang, Jin-Fu Wu, Suchada Saovieng, Wei-Horng Chien, Ming-Fen Hsu, Xiao-Fei Li, Shin-Da Lee, Chih-Yang Huang, Chih-Yang Huang, Chia-Hua Kuo

Doxorubicin inhibits muscle inflammation after eccentric exerciseBackground
Doxorubicin, a widely used anti-tumour drug, is known to cause muscle loss in cancer patients.
Methods
Following an acute dose of doxorubicin injection (2.5 mg/kg per body weight), we examined macrophage distribution in rat soleus muscle challenged by eccentric exercise (downhill running). Long-term doxorubicin treatment (one injection every 3 days) on muscle mass and survival were also determined.
Results
Under non-exercised condition, increased tumour necrosis factor (TNF)-alpha mRNA and decreased IL-10 mRNA were observed in soleus muscle of doxorubicin-treated rats, compared with saline-treated control rats. However, increases in inflammation score (leukocyte infiltration), nitrotyrosine level, and M1 macrophage (CD68+) invasion in exercised soleus muscle were absent in doxorubicin-treated rats, whereas increased M2 macrophage (CD163+) localization in exercised muscle was less affected by doxorubicin. Despites coenzyme Q (Q10) supplementation significantly elevated TNF-alpha mRNA, nitrotyrosine, and anti-oxidant gamma-glutamylcysteine synthetase (GCS) levels in non-exercised soleus muscle, these pro-inflammatory responses were also abolished in doxorubicin-treated rats. Results from long-term doxorubicin treatment show a significant muscle loss followed by an accelerated death, which cannot be reversed by Q10 supplementation.
Conclusions
(i) Doxorubicin impairs inflammation mechanism by depleting M1 macrophage in exercised skeletal muscle; (ii) Muscle loss and accelerated death during prolonged doxorubicin treatment cannot be reversed by Q10 supplementation.

 

Huang, S. -C., Wu, J. -F., Saovieng, S., Chien, W. -H., Hsu, M. -F., Li, X. -F., Lee, S. -D., Huang, C. -Y., Huang, C. -Y., and Kuo, C. -H. (2016) Doxorubicin inhibits muscle inflammation after eccentric exercise. Journal of Cachexia, Sarcopenia and Muscle, doi: 10.1002/jcsm.12148.

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     Article first published online:  8 OCT 2016

Christopher Lipina, Harinder S Hundal

Lipid modulation of skeletal muscle mass and functionLoss of skeletal muscle mass is a characteristic feature of various pathologies including cancer, diabetes, and obesity, as well as being a general feature of ageing. However, the processes underlying its pathogenesis are not fully understood and may involve multiple factors. Importantly, there is growing evidence which supports a role for fatty acids and their derived lipid intermediates in the regulation of skeletal muscle mass and function. In this review, we discuss evidence pertaining to those pathways which are involved in the reduction, increase and/or preservation of skeletal muscle mass by such lipids under various pathological conditions, and highlight studies investigating how these processes may be influenced by dietary supplementation as well as genetic and/or pharmacological intervention.

 

Lipina, C., and Hundal, H. S. (2016) Lipid modulation of skeletal muscle mass and function. Journal of Cachexia, Sarcopenia and Muscle, doi: 10.1002/jcsm.12144.

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     Article first published online:  5 OCT 2016

Jinhee Kim, Yunhwan Lee, Seunghee Kye, Yoon-Sok Chung, Okhee Lee

Association of serum vitamin D with osteosarcopenic obesity: Korea National Health and Nutrition Examination Survey 2008–2010Background
Serum vitamin D levels have been reported to be associated with individual components of body composition. However, the relationship between serum vitamin D and combined indices of adverse body composition is largely unknown. This cross-sectional study examined the association between serum vitamin D and osteosarcopenic obesity in a nationally representative sample of middle-aged and older adults.
Methods
We analysed the Korea National Health and Nutrition Examination Surveys (IV and V) conducted in 2008–2010, consisting of 5908 (2485 men, 3423 women) aged =?50?years. Serum vitamin D levels were determined by radioimmunoassay, and body composition was evaluated by dual-energy x-ray absorptiometry. The association between serum vitamin D levels and the number of abnormalities in body composition, including osteosarcopenic obesity, a low bone and muscle mass with concurrent high fat mass, was analysed by multinomial logistic regression adjusting for covariates.
Results
In men, after controlling for covariates, higher vitamin D levels were associated with a significantly reduced likelihood of the number of phenotypes of adverse body composition (P for trend?<?0.05). Those in the highest tertile group of serum vitamin D levels, compared with those in the lowest tertile, were less likely to have adverse body composition, numbering one (odds ratio [OR]?=?0.67, 95% confidence interval [CI]: 0.49, 0.92), two (OR?=?0.49, 95% CI: 0.33, 0.73), and three (osteosarcopenic obesity; OR?=?0.42, 95% CI: 0.26, 0.67). In women, those in the highest tertile group of serum vitamin D levels, compared with those in the lowest tertile, were less likely to have osteosarcopenic obesity (OR?=?0.55, 95% CI: 0.33, 0.93). Vitamin D deficiency (<20?ng/mL) in men was significantly associated with an increased likelihood of a higher number of adverse body composition, especially for osteosarcopenic obesity (OR?=?2.08, 95% CI: 1.42, 3.03). Vitamin D deficient women, compared with those having normal levels of serum vitamin D, were also more likely to demonstrate osteosarcopenic obesity (OR?=?1.99, 95% CI: 1.30, 3.05).
Conclusions
A high serum vitamin D level in mid- and late-life was associated with reduced odds of multiple adverse body composition, especially osteosarcopenic obesity, suggesting potential health benefits of maintaining adequate levels of vitamin D.

 

Kim, J., Lee, Y., Kye, S., Chung, Y. -S., and Lee, O. (2016) Association of serum vitamin D with osteosarcopenic obesity: Korea National Health and Nutrition Examination Survey 2008–2010. Journal of Cachexia, Sarcopenia and Muscle, doi: 10.1002/jcsm.12154.

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     Article first published online: 16 SEP 2016

Hui Ding, Guohua Zhang, Ka Wai Thomas Sin, Zhelong Liu, Ren-Kuo Lin, Min Li, Yi-Ping Li

Activin A induces skeletal muscle catabolism via p38β mitogen-activated protein kinasesBackground
Activation of type IIB activin receptor (ActRIIB) in skeletal muscle leads to muscle atrophy because of increased muscle protein degradation. However, the intracellular signalling mechanism that mediates ActRIIB-activated muscle catabolism is poorly defined.
Methods
We investigated the role of p38β mitogen-activated protein kinases (MAPK) in mediating ActRIIB ligand activin A-activated muscle catabolic pathways in C2C12 myotubes and in mice with perturbation of this kinase pharmacologically and genetically.
Results
Treatment of C2C12 myotubes with activin A or myostatin rapidly activated p38 MAPK and its effector C/EBPβ within 1 h. Paradoxically, Akt was activated at the same time through a p38 MAPK-independent mechanism. These events were followed by up-regulation of ubiquitin ligases atrogin1 (MAFbx) and UBR2 (E3α-II), as well as increase in LC3-II, a marker of autophagosome formation, leading to myofibrillar protein loss and myotube atrophy. The catabolic effects of activin A were abolished by p38α/β MAPK inhibitor SB202190. Using small interfering RNA-mediated gene knockdown, we found that the catabolic activity of activin A was dependent on p38β MAPK specifically. Importantly, systemic administration of activin A to mice similarly activated the catabolic pathways in vivo, and this effect was blocked by SB202190. Further, activin A failed to activate the catabolic pathways in mice with muscle-specific knockout of p38β MAPK. Interestingly, activin A up-regulated MuRF1 in a p38 MAPK-independent manner, and MuRF1 did not appear responsible for activin A-induced myosin heavy chain loss and muscle atrophy.
Conclusions
ActRIIB-mediated activation of muscle catabolism is dependent on p38β MAPK-activated signalling.

 

Ding, H., Zhang, G., Sin, K. W. T., Liu, Z., Lin, R. -K., Li, M., and Li, Y. -P. (2016) Activin A induces skeletal muscle catabolism via p38β mitogen-activated protein kinases. Journal of Cachexia, Sarcopenia and Muscle, doi: 10.1002/jcsm.12145.

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     Article first published online: 2 SEP 2016

Félix St-Jean-Pelletier, Charlotte H Pion, Jean-Philippe Leduc-Gaudet, Nicolas Sgarioto, Igor Zovilé, Sébastien Barbat-Artigas, Olivier Reynaud, Feras Alkaterji, François C Lemieux, Alexis Grenon, Pierrette Gaudreau, Russell T Hepple, Stéphanie Chevalier, Marc Belanger, José A Morais, Mylène Aubertin-Leheudre, Gilles Gouspillou

The impact of ageing, physical activity, and pre-frailty on skeletal muscle phenotype, mitochondrial content, and intramyocellular lipids in menBackground
The exact impact of ageing on skeletal muscle phenotype and mitochondrial and lipid content remains controversial, probably because physical activity, which greatly influences muscle physiology, is rarely accounted for. The present study was therefore designed to investigate the effects of ageing, physical activity, and pre-frailty on skeletal muscle phenotype, and mitochondrial and intramyocellular lipid content in men.
Methods
Recreationally active young adult (20–30 yo; YA); active (ACT) and sedentary (SED) middle-age (50–65 yo; MA-ACT and MA-SED); and older (65 + yo; 65 + ACT and 65 + SED) and pre-frail older (65 + PF) men were recruited. Muscle biopsies from the vastus lateralis were collected to assess, on muscle cross sections, muscle phenotype (using myosin heavy chain isoforms immunolabelling), the fibre type-specific content of mitochondria (by quantifying the succinate dehydrogenase stain intensity), and the fibre type-specific lipid content (by quantifying the Oil Red O stain intensity).
Results
Only 65 + SED and 65 + PF displayed significantly lower overall and type IIa fibre sizes vs. YA. 65 + SED displayed a lower type IIa fibre proportion vs. YA. MA-SED and 65 + SED displayed a higher hybrid type IIa/IIx fibre proportion vs. YA. Sedentary and pre-frail, but not active, men displayed lower mitochondrial content irrespective of fibre type vs. YA. 65 + SED, but not 65 + ACT, displayed a higher lipid content in type I fibres vs. YA. Finally, mitochondrial content, but not lipid content, was positively correlated with indices of muscle function, functional capacity, and insulin sensitivity across all subjects.
Conclusions
Taken altogether, our results indicate that ageing in sedentary men is associated with (i) complex changes in muscle phenotype preferentially affecting type IIa fibres; (ii) a decline in mitochondrial content affecting all fibre types; and (iii) an increase in lipid content in type I fibres. They also indicate that physical activity partially protects from the effects of ageing on muscle phenotype, mitochondrial content, and lipid accumulation. No skeletal specific muscle phenotype of pre-frailty was observed.

 

 

St-Jean-Pelletier, F., Pion, C. H., Leduc-Gaudet, J. -P., Sgarioto, N., Zovilé, I., Barbat-Artigas, S., Reynaud, O., Alkaterji, F., Lemieux, F. C., Grenon, A., Gaudreau, P., Hepple, R. T., Chevalier, S., Belanger, M., Morais, J. A., Aubertin-Leheudre, M., and Gouspillou, G. (2016) The impact of ageing, physical activity, and pre-frailty on skeletal muscle phenotype, mitochondrial content, and intramyocellular lipids in men. Journal of Cachexia, Sarcopenia and Muscle, doi: 10.1002/jcsm.12139.

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     Article first published online: 4 AUG 2016

Tim Snijders, Joshua P. Nederveen, Sophie Joanisse, Marika Leenders, Lex B. Verdijk, Luc J.C. van Loon, Gianni Parise

Muscle fibre capillarization is a critical factor in muscle fibre hypertrophy during resistance exercise training in older menBackground
Adequate muscle fibre perfusion is critical for the maintenance of muscle mass; it is essential in the rapid delivery of oxygen, nutrients and growth factors to the muscle, stimulating muscle fibre growth. Muscle fibre capillarization is known to decrease substantially with advancing age. However, whether (relative) low muscle fibre capillarization negatively impacts the muscle hypertrophic response following resistance exercise training in older adults is unknown.
Methods
Twenty-two healthy older men (71 ± 1 years) performed 24 weeks of progressive resistance type exercise training. To assess the change in muscle fibre characteristics, percutaneous biopsies from the vastus lateralis muscle were taken before and following 12 and 24 weeks of the intervention programme. A comparison was made between participants who had a relatively low type II muscle fibre capillary-to-fibre perimeter exchange index (CFPE; LOW group) and high type II muscle fibre CFPE (HIGH group) at baseline. Type I and type II muscle fibre size, satellite cell, capillary content and distance between satellite cells to the nearest capillary were determined by immunohistochemistry.
Results
Overall, type II muscle fibre size (from 5150 ± 234 to 6719 ± 446 µm2, P < 0.05) and satellite cell content (from 0.058 ± 0.006 to 0.090 ± 0.010 satellite cells per muscle fibre, P  < 0.05) had increased significantly in response to 24 weeks of resistance exercise training. However, these improvements where mainly driven by differences in baseline type II muscle fibre capillarization, whereas muscle fibre size (from 5170 ± 390 to 7133 ± 314 µm2, P < 0.05) and satellite cell content (from 0.059 ± 0.009 to 0.102 ± 0.017 satellite cells per muscle fibre, P  < 0.05) increased significantly in the HIGH group, no significant changes were observed in LOW group following exercise training. No significant changes in type I and type II muscle fibre capillarization were observed in response to 12 and 24 weeks of resistance exercise training in both the LOW and HIGH group.
Conclusions
Type II muscle fibre capillarization at baseline may be a critical factor for allowing muscle fibre hypertrophy to occur during prolonged resistance exercise training in older men.

 

Snijders, T., Nederveen, J. P., Joanisse, S., Leenders, M., Verdijk, L. B., van Loon, L. J. C., and Parise, G. (2016) Muscle fibre capillarization is a critical factor in muscle fibre hypertrophy during resistance exercise training in older men. Journal of Cachexia, Sarcopenia and Muscle, doi: 10.1002/jcsm.12137.

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