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17 results on '"Cécile Coudy-Gandilhon"'

1. Induction of ATF4-Regulated Atrogenes Is Uncoupled from Muscle Atrophy during Disuse in Halofuginone-Treated Mice and in Hibernating Brown Bears

Author

Laura Cussonneau, Cécile Coudy-Gandilhon, Christiane Deval, Ghita Chaouki, Mehdi Djelloul-Mazouz, Yoann Delorme, Julien Hermet, Guillemette Gauquelin-Koch, Cécile Polge, Daniel Taillandier, Julien Averous, Alain Bruhat, Céline Jousse, Isabelle Papet, Fabrice Bertile, Etienne Lefai, Pierre Fafournoux, Anne-Catherine Maurin, and Lydie Combaret

Subjects
skeletal muscle, unloading, hindlimb suspension, halofuginone, ATF4, TGF-β/BMP signalling, Biology (General), QH301-705.5, Chemistry, QD1-999
Abstract

Activating transcription factor 4 (ATF4) is involved in muscle atrophy through the overexpression of some atrogenes. However, it also controls the transcription of genes involved in muscle homeostasis maintenance. Here, we explored the effect of ATF4 activation by the pharmacological molecule halofuginone during hindlimb suspension (HS)-induced muscle atrophy. Firstly, we reported that periodic activation of ATF4-regulated atrogenes (Gadd45a, Cdkn1a, and Eif4ebp1) by halofuginone was not associated with muscle atrophy in healthy mice. Secondly, halofuginone-treated mice even showed reduced atrophy during HS, although the induction of the ATF4 pathway was identical to that in untreated HS mice. We further showed that halofuginone inhibited transforming growth factor-β (TGF-β) signalling, while promoting bone morphogenetic protein (BMP) signalling in healthy mice and slightly preserved protein synthesis during HS. Finally, ATF4-regulated atrogenes were also induced in the atrophy-resistant muscles of hibernating brown bears, in which we previously also reported concurrent TGF-β inhibition and BMP activation. Overall, we show that ATF4-induced atrogenes can be uncoupled from muscle atrophy. In addition, our data also indicate that halofuginone can control the TGF-β/BMP balance towards muscle mass maintenance. Whether halofuginone-induced BMP signalling can counteract the effect of ATF4-induced atrogenes needs to be further investigated and may open a new avenue to fight muscle atrophy. Finally, our study opens the way for further studies to identify well-tolerated chemical compounds in humans that are able to fine-tune the TGF-β/BMP balance and could be used to preserve muscle mass during catabolic situations.

Published
2022
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2. Activation of the eIF2α-ATF4 Pathway by Chronic Paracetamol Treatment Is Prevented by Dietary Supplementation with Cysteine

Author

Valérie Carraro, Lydie Combaret, Cécile Coudy-Gandilhon, Laurent Parry, Julien Averous, Anne-Catherine Maurin, Céline Jousse, Guillaume Voyard, Pierre Fafournoux, Isabelle Papet, and Alain Bruhat

Subjects
acetaminophen, eIF2α-ATF4 pathway, GCN2, cysteine, liver, skeletal muscle, Biology (General), QH301-705.5, Chemistry, QD1-999
Abstract

Chronic treatment with acetaminophen (APAP) induces cysteine (Cys) and glutathione (GSH) deficiency which leads to adverse metabolic effects including muscle atrophy. Mammalian cells respond to essential amino acid deprivation through the phosphorylation of the eukaryotic translation initiation factor 2α (eIF2α). Phosphorylated eIF2α leads to the recruitment of activating transcription factor 4 (ATF4) to specific CCAAT/enhancer-binding protein-ATF response element (CARE) located in the promoters of target genes. Our purpose was to study the activation of the eIF2α-ATF4 pathway in response to APAP-induced Cys deficiency, as well as the potential contribution of the eIF2α kinase GCN2 and the effect of dietary supplementation with Cys. Our results showed that chronic treatment with APAP activated both GCN2 and PERK eIF2α kinases and downstream target genes in the liver. Activation of the eIF2α-ATF4 pathway in skeletal muscle was accompanied by muscle atrophy even in the absence of GCN2. The dietary supplementation with cysteine reversed APAP-induced decreases in plasma-free Cys, liver GSH, muscle mass, and muscle GSH. Our new findings demonstrate that dietary Cys supplementation also reversed the APAP-induced activation of GCN2 and PERK and downstream ATF4-target genes in the liver.

Published
2022
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3. A Single Bout of Ultra-Endurance Exercise Reveals Early Signs of Muscle Aging in Master Athletes

Author

Cécile Coudy-Gandilhon, Marine Gueugneau, Christophe Chambon, Daniel Taillandier, Lydie Combaret, Cécile Polge, Guillaume Y. Millet, Léonard Féasson, and Daniel Béchet

Subjects
aging, exercise, skeletal muscle, capillaries, lipid droplets, extracellular matrix, Biology (General), QH301-705.5, Chemistry, QD1-999
Abstract

Middle-aged and master endurance athletes exhibit similar physical performance and long-term muscle adaptation to aerobic exercise. Nevertheless, we hypothesized that the short-term plasticity of the skeletal muscle might be distinctly altered for master athletes when they are challenged by a single bout of prolonged moderate-intensity exercise. Six middle-aged (37Y) and five older (50Y) master highly-trained athletes performed a 24-h treadmill run (24TR). Vastus lateralis muscle biopsies were collected before and after the run and assessed for proteomics, fiber morphometry, intramyocellular lipid droplets (LD), mitochondrial oxidative activity, extracellular matrix (ECM), and micro-vascularisation. Before 24TR, muscle fiber type morphometry, intramyocellular LD, oxidative activity, ECM and micro-vascularisation were similar between master and middle-aged runners. For 37Y runners, 24TR was associated with ECM thickening, increased capillary-to-fiber interface, and an 89% depletion of LD in type-I fibers. In contrast, for 50Y runners, 24TR did not alter ECM and capillarization and poorly depleted LDs. Moreover, an impaired succinate dehydrogenase activity and functional class scoring of proteomes suggested reduced oxidative phosphorylation post-24TR exclusively in 50Y muscle. Collectively, our data support that middle-aged and master endurance athletes exhibit distinct transient plasticity in response to a single bout of ultra-endurance exercise, which may constitute early signs of muscle aging for master athletes.

Published
2022
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4. Magnesium Deficiency Alters Expression of Genes Critical for Muscle Magnesium Homeostasis and Physiology in Mice

Author

Dominique Bayle, Cécile Coudy-Gandilhon, Marine Gueugneau, Sara Castiglioni, Monica Zocchi, Magdalena Maj-Zurawska, Adriana Palinska-Saadi, André Mazur, Daniel Béchet, and Jeanette A. Maier

Subjects
skeletal muscle, magnesium, magnesium transporters, transcriptome, Nutrition. Foods and food supply, TX341-641
Abstract

Chronic Mg2+ deficiency is the underlying cause of a broad range of health dysfunctions. As 25% of body Mg2+ is located in the skeletal muscle, Mg2+ transport and homeostasis systems (MgTHs) in the muscle are critical for whole-body Mg2+ homeostasis. In the present study, we assessed whether Mg2+ deficiency alters muscle fiber characteristics and major pathways regulating muscle physiology. C57BL/6J mice received either a control, mildly, or severely Mg2+-deficient diet (0.1%; 0.01%; and 0.003% Mg2+ wt/wt, respectively) for 14 days. Mg2+ deficiency slightly decreased body weight gain and muscle Mg2+ concentrations but was not associated with detectable variations in gastrocnemius muscle weight, fiber morphometry, and capillarization. Nonetheless, muscles exhibited decreased expression of several MgTHs (MagT1, CNNM2, CNNM4, and TRPM6). Moreover, TaqMan low-density array (TLDA) analyses further revealed that, before the emergence of major muscle dysfunctions, even a mild Mg2+ deficiency was sufficient to alter the expression of genes critical for muscle physiology, including energy metabolism, muscle regeneration, proteostasis, mitochondrial dynamics, and excitation–contraction coupling.

Published
2021
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5. Muscle Proteomic and Transcriptomic Profiling of Healthy Aging and Metabolic Syndrome in Men

Author

Marine Gueugneau, Cécile Coudy-Gandilhon, Christophe Chambon, Julien Verney, Daniel Taillandier, Lydie Combaret, Cécile Polge, Stéphane Walrand, Frédéric Roche, Jean-Claude Barthélémy, Léonard Féasson, and Daniel Béchet

Subjects
skeletal muscle, aging, sarcopenia, metabolic syndrome, proteome, transcriptome, Biology (General), QH301-705.5, Chemistry, QD1-999
Abstract

(1) Background: Aging is associated with a progressive decline in muscle mass and function. Aging is also a primary risk factor for metabolic syndrome, which further alters muscle metabolism. However, the molecular mechanisms involved remain to be clarified. Herein we performed omic profiling to decipher in muscle which dominating processes are associated with healthy aging and metabolic syndrome in old men. (2) Methods: This study included 15 healthy young, 15 healthy old, and 9 old men with metabolic syndrome. Old men were selected from a well-characterized cohort, and each vastus lateralis biopsy was used to combine global transcriptomic and proteomic analyses. (3) Results: Over-representation analysis of differentially expressed genes (ORA) and functional class scoring of pathways (FCS) indicated that healthy aging was mainly associated with upregulations of apoptosis and immune function and downregulations of glycolysis and protein catabolism. ORA and FCS indicated that with metabolic syndrome the dominating biological processes were upregulation of proteolysis and downregulation of oxidative phosphorylation. Proteomic profiling matched 586 muscle proteins between individuals. The proteome of healthy aging revealed modifications consistent with a fast-to-slow transition and downregulation of glycolysis. These transitions were reduced with metabolic syndrome, which was more associated with alterations in NADH/NAD+ shuttle and β-oxidation. Proteomic profiling further showed that all old muscles overexpressed protein chaperones to preserve proteostasis and myofiber integrity. There was also evidence of aging-related increases in reactive oxygen species but better detoxifications of cytotoxic aldehydes and membrane protection in healthy than in metabolic syndrome muscles. (4) Conclusions: Most candidate proteins and mRNAs identified herein constitute putative muscle biomarkers of healthy aging and metabolic syndrome in old men.

Published
2021
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6. Mitophagy and Mitochondria Biogenesis Are Differentially Induced in Rat Skeletal Muscles during Immobilization and/or Remobilization

Author

Christiane Deval, Julie Calonne, Cécile Coudy-Gandilhon, Emilie Vazeille, Daniel Bechet, Cécile Polge, Daniel Taillandier, Didier Attaix, and Lydie Combaret

Subjects
immobilization, recovery, mitophagy, microtubules, physical inactivity, skeletal muscle, Biology (General), QH301-705.5, Chemistry, QD1-999
Abstract

Mitochondria alterations are a classical feature of muscle immobilization, and autophagy is required for the elimination of deficient mitochondria (mitophagy) and the maintenance of muscle mass. We focused on the regulation of mitochondrial quality control during immobilization and remobilization in rat gastrocnemius (GA) and tibialis anterior (TA) muscles, which have very different atrophy and recovery kinetics. We studied mitochondrial biogenesis, dynamic, movement along microtubules, and addressing to autophagy. Our data indicated that mitochondria quality control adapted differently to immobilization and remobilization in GA and TA muscles. Data showed i) a disruption of mitochondria dynamic that occurred earlier in the immobilized TA, ii) an overriding role of mitophagy that involved Parkin-dependent and/or independent processes during immobilization in the GA and during remobilization in the TA, and iii) increased mitochondria biogenesis during remobilization in both muscles. This strongly emphasized the need to consider several muscle groups to study the mechanisms involved in muscle atrophy and their ability to recover, in order to provide broad and/or specific clues for the development of strategies to maintain muscle mass and improve the health and quality of life of patients.

Published
2020
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7. A Proof of Concept to Bridge the Gap between Mass Spectrometry Imaging, Protein Identification and Relative Quantitation: MSI~LC-MS/MS-LF

Author

Laëtitia Théron, Delphine Centeno, Cécile Coudy-Gandilhon, Estelle Pujos-Guillot, Thierry Astruc, Didier Rémond, Jean-Claude Barthelemy, Frédéric Roche, Léonard Feasson, Michel Hébraud, Daniel Béchet, and Christophe Chambon

Subjects
MALDI mass spectrometry imaging, protein identification, label-free quantitation, skeletal muscle, Microbiology, QR1-502
Abstract

Mass spectrometry imaging (MSI) is a powerful tool to visualize the spatial distribution of molecules on a tissue section. The main limitation of MALDI-MSI of proteins is the lack of direct identification. Therefore, this study focuses on a MSI~LC-MS/MS-LF workflow to link the results from MALDI-MSI with potential peak identification and label-free quantitation, using only one tissue section. At first, we studied the impact of matrix deposition and laser ablation on protein extraction from the tissue section. Then, we did a back-correlation of the m/z of the proteins detected by MALDI-MSI to those identified by label-free quantitation. This allowed us to compare the label-free quantitation of proteins obtained in LC-MS/MS with the peak intensities observed in MALDI-MSI. We managed to link identification to nine peaks observed by MALDI-MSI. The results showed that the MSI~LC-MS/MS-LF workflow (i) allowed us to study a representative muscle proteome compared to a classical bottom-up workflow; and (ii) was sparsely impacted by matrix deposition and laser ablation. This workflow, performed as a proof-of-concept, suggests that a single tissue section can be used to perform MALDI-MSI and protein extraction, identification, and relative quantitation.

Published
2016
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8. Lipid accumulation and mitochondrial abnormalities are associated with fiber atrophy in skeletal muscle of rats with collagen-induced arthritis

Author

Frédéric Capel, Gaëlle Vial, Fabien Wauquier, Carole Chevenet, Alexandre Pinel, Martin Soubrier, Cécile Coudy-Gandilhon, Yohan Wittrant, Daniel Béchet, Anne Tournadre, Véronique Coxam, Service de rhumatologie, CHU Clermont-Ferrand, Unité de Nutrition Humaine (UNH), Université Clermont Auvergne [2017-2020] (UCA [2017-2020])-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Laboratoire d'Anatomie et de Cytologie Pathologique, Groupe Hospitalier de l'Institut Catholique de Lille (GHICL), public grant (ARTH-INNOV project) from the European Regional Development Fund (ERDF/FEDER-Region Auvergne), Groupement des Hôpitaux de l'Institut Catholique de Lille (GHICL), Université catholique de Lille (UCL)-Université catholique de Lille (UCL), Unité de Nutrition Humaine - Clermont Auvergne (UNH), Institut National de la Recherche Agronomique (INRA)-Université Clermont Auvergne (UCA), and Groupement hospitalier de l'Institut Catholique de Lille

Subjects
0301 basic medicine, Male, medicine.medical_specialty, Sarcopenia, Ubiquitin-Protein Ligases, Freund's Adjuvant, Muscle Fibers, Skeletal, Adipose tissue, Arthritis, Muscle Proteins, Arthritis, Rheumatoid, Rats, Sprague-Dawley, Tripartite Motif Proteins, 03 medical and health sciences, Gastrocnemius muscle, 0302 clinical medicine, Atrophy, Tibialis anterior muscle, Internal medicine, medicine, Animals, Humans, Rats, Wistar, Molecular Biology, Collagen Type II, Triglycerides, SKP Cullin F-Box Protein Ligases, Myogenesis, business.industry, Skeletal muscle, Cell Biology, medicine.disease, Arthritis, Experimental, Lipids, Rats, Mitochondria, PPAR gamma, Muscular Atrophy, 030104 developmental biology, Endocrinology, medicine.anatomical_structure, Adipose Tissue, Muscle, business, [SDV.AEN]Life Sciences [q-bio]/Food and Nutrition, 030217 neurology & neurosurgery
Abstract

Epub ahead of print; Rheumatoid arthritis (RA) has a negative impact on muscle mass, and reduces patient's mobility and autonomy. Furthermore, RA is associated with metabolic comorbidities, notably in lipid homeostasis by unknown mechanisms. To understand the links between the loss in muscle mass and the metabolic abnormalities, arthritis was induced in male Sprague Dawley rats (n=11) using the collagen-induced arthritis model. Rats immunized with bovine type II collagen were compared to a control group of animals (n=11) injected with acetic acid and complete Freund's adjuvant. The clinical severity of the ensuing arthritis was evaluated weekly by a semi-quantitative score. Skeletal muscles from the hind limb were used for the histological analysis and exploration of mitochondrial activity, lipid accumulation, metabolism and regenerative capacities A significant atrophy in tibialis anterior muscle fibers was observed in rats with arthritis despite a non-significant decrease in the weight of the muscles. Despite moderate inflammation, accumulation of triglycerides (P

Published
2020

9. Increased Serpina3n release into circulation during glucocorticoid-mediated muscle atrophy

Author

Dominique Maiter, Donatienne d'Hose, Yann-Gaël Gangloff, Laure B. Bindels, Caroline Barbé, Laurent Schaeffer, Christophe Chambon, Marine Gueugneau, Nathalie M. Delzenne, Daniel Béchet, Cécile Coudy-Gandilhon, Pascale Lause, Marie de Barsy, and Jean-Paul Thissen

Subjects
0301 basic medicine, medicine.medical_specialty, Myostatin, Muscle hypertrophy, 03 medical and health sciences, Physiology (medical), Internal medicine, Diabetes mellitus, medicine, Myocyte, Orthopedics and Sports Medicine, biology, business.industry, Skeletal muscle, medicine.disease, Muscle atrophy, 3. Good health, 030104 developmental biology, medicine.anatomical_structure, Endocrinology, biology.protein, Biomarker (medicine), medicine.symptom, business, Glucocorticoid, medicine.drug
Abstract

BACKGROUND: Glucocorticoids (GC) play a major role in muscle atrophy. As skeletal muscle is a secretory organ, characterization of the muscle secretome elicited by muscle atrophy should allow to better understand the cellular mechanisms and to identify circulating biomarkers of this condition. Our project aimed to identify the changes in the muscle secretome associated with GC-induced muscle atrophy and susceptible to translate into circulation. METHODS: We have identified the GC-induced changes in the secretome of C2 C12 muscle cells by proteomic analysis, and then, we have determined how these changes translate into the circulation of mice or human subjects exposed to high concentrations of GC. RESULTS: This approach led us to identify Serpina3n as one of the most markedly secreted protein in response to GC. Our original in vitro results were confirmed in vivo by an increased expression of Serpina3n in skeletal muscle (3.9-fold; P < 0.01) and in the serum (two-fold; P < 0.01) of mice treated with GC. We also observed increased levels of the human orthologue Serpina3 in the serum of Cushing's syndrome patients compared with healthy controls matched for age and sex (n = 9/group, 2.5-fold; P < 0.01). An increase of Serpina3n was also demonstrated in muscle atrophy models mediated by GC such as cancer cachexia (four-fold; P < 0.01), sepsis (12.5-fold; P < 0.001), or diabetes (two-fold; P < 0.01). In contrast, levels of Serpina3n both in skeletal muscle and in the circulation were reduced in several models of muscle hypertrophy induced by myostatin inhibition (P < 0.01). Furthermore, a cluster of data suggests that the regulation of muscle Serpina3n involves mTOR, an essential determinant of the muscle cell size. CONCLUSIONS: Taken together, these data suggest that Serpina3n may represent a circulating biomarker of muscle atrophy associated to GC and, broadly, a reflection of dynamic changes in muscle mass.

Published
2018

10. Beneficial effects of endurance exercise training on skeletal muscle microvasculature in sickle cell disease patients

Author

Pablo Bartolucci, Frédéric Galactéros, Léonard Féasson, Thomas Rupp, Cécile Coudy-Gandilhon, Laurent Messonnier, Barnabas Gellen, Daniel Béchet, Angèle N. Merlet, Laboratoire Interuniversitaire de Biologie de la Motricité, Université Savoie Mont Blanc (USMB [Université de Savoie] [Université de Chambéry]), Unité de Nutrition Humaine (UNH), Institut National de la Recherche Agronomique (INRA)-Université Clermont Auvergne [2017-2020] (UCA [2017-2020]), ELSAN-Polyclinique de Poitiers, CHU Henri Mondor, CHU Henri Mondor AP-HP/UPEC, CHU de St Etienne, Unité de Nutrition Humaine - Clermont Auvergne (UNH), Institut National de la Recherche Agronomique (INRA)-Université Clermont Auvergne (UCA), CHU Henri Mondor [Créteil], and Centre Hospitalier Universitaire de Saint-Etienne [CHU Saint-Etienne] (CHU ST-E)

Subjects
medicine.medical_specialty, Vastus lateralis muscle, Anemia, Immunology, education, 030204 cardiovascular system & hematology, Biochemistry, law.invention, Incremental exercise, 03 medical and health sciences, 0302 clinical medicine, Randomized controlled trial, Endurance training, law, Internal medicine, Biopsy, medicine, 030304 developmental biology, 0303 health sciences, medicine.diagnostic_test, business.industry, Skeletal muscle, Cell Biology, Hematology, medicine.disease, 3. Good health, Hemoglobinopathy, medicine.anatomical_structure, Cardiology, business, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology
Abstract

Epub ahead of print; Sickle cell disease (SCD) is a genetic hemoglobinopathy leading to two major clinical manifestations: severe chronic hemolytic anemia and iterative vaso-occlusive crises. SCD is also accompanied by profound muscle microvascular remodeling. The beneficial effects of endurance training on microvasculature are widely known. The aim of this study was to evaluate the effects of an endurance training program on microvasculature of skeletal muscle in SCD patients. A biopsy of the vastus lateralis muscle and submaximal incremental exercise were performed before and after the training period. Of the forty randomized SCD patients, complete data sets from 32 were obtained. The training group (n=15) followed a personalized moderate-intensity endurance training program, while the non-training (n=17) group maintained a normal lifestyle. Training consisted of three 40-minute cycle ergometer exercise sessions per week for 8 weeks. Histological analysis highlighted microvascular benefits in the training SCD patients compared to non-training patients, including increases in capillary density (CD) (P = .003), number of capillaries around a fiber (CAF) (P = .015) and functional exchange surface (LC/PF) (P < .0001). Conversely, no significant between-group difference was found in the morphology of capillaries. Indexes of physical ability also improved in the training patients. The moderate-intensity endurance exercise training program improved the muscle capillary network and partly reversed the microvascular defects commonly observed in skeletal muscle of SCD patients. This trial was registered at www.clinicaltrials.gov as #NCT02571088.

Published
2019

11. Erratum: Polge, C., et al. UBE2E1 Is Preferentially Expressed in the Cytoplasm of Slow-Twitch Fibers and Protects Skeletal Muscles from Exacerbated Atrophy upon Dexamethasone Treatment. Cells 2018, 7, 214

Author

Cécile Polge, Lydie Combaret, Cécile Coudy-Gandilhon, Christiane Deval, Daniel Béchet, Clara Tournebize, Didier Attaix, Agnès Claustre, Julien Aniort, Marco Sandri, Andrea Armani, and Daniel Taillandier

Subjects
0301 basic medicine, medicine.medical_specialty, UBE2E1, E3 ubiquitin ligases, Article, 03 medical and health sciences, myosin heavy chain, Atrophy, atrophy, Internal medicine, medicine, skeletal muscle, lcsh:QH301-705.5, Dexamethasone, Chemistry, E2 ubiquitin-conjugating enzymes, General Medicine, medicine.disease, MuRF1, 030104 developmental biology, Endocrinology, n/a, lcsh:Biology (General), Cytoplasm, Erratum, ubiquitin-proteasome system, actin, medicine.drug
Abstract

Skeletal muscle mass is reduced during many diseases or physiological situations (disuse, aging), which results in decreased strength and increased mortality. Muscle mass is mainly controlled by the ubiquitin-proteasome system (UPS), involving hundreds of ubiquitinating enzymes (E2s and E3s) that target their dedicated substrates for subsequent degradation. We recently demonstrated that MuRF1, an E3 ubiquitin ligase known to bind to sarcomeric proteins (telethonin, α-actin, myosins) during catabolic situations, interacts with 5 different E2 enzymes and that these E2-MuRF1 couples are able to target telethonin, a small sarcomeric protein, for degradation. Amongst the E2s interacting with MuRF1, E2E1 was peculiar as the presence of the substrate was necessary for optimal MuRF1-E2E1 interaction. In this work, we focused on the putative role of E2E1 during skeletal muscle atrophy. We found that E2E1 expression was restricted to type I and type IIA muscle fibers and was not detectable in type IIB fibers. This strongly suggests that E2E1 targets are fiber-specific and may be strongly linked to the contractile and metabolic properties of the skeletal muscle. However, E2E1 knockdown was not sufficient for preserving the protein content in C2C12 myotubes subjected to a catabolic state (dexamethasone treatment), suggesting that E2E1 is not involved in the development of muscle atrophy. By contrast, E2E1 knockdown aggravated the atrophying process in both catabolic C2C12 myotubes and the Tibialis anterior muscle of mice, suggesting that E2E1 has a protective effect on muscle mass.

Published
2018

12. Abstracts of the 7th Cachexia Conference, Kobe/Osaka, Japan, December 9-11, 2013 (Part 2)

Author

Cécile Polge, Didier Attaix, Huijuan Wang, Lydie Combaret, Anne Listrat, Daniel Taillandier, Cécile Coudy-Gandilhon, Kijoon Lee, Claire Lethias, Bruno Meunier, Daniel Béchet, Marine Gueugneau, and Kheng Lim Goh

Subjects
0303 health sciences, Stromal cell, TUNEL assay, Angiogenesis, Chemistry, Skeletal muscle, 030204 cardiovascular system & hematology, musculoskeletal system, medicine.disease, Article, Cell biology, 03 medical and health sciences, Gastrocnemius muscle, 0302 clinical medicine, Atrophy, medicine.anatomical_structure, Apoptosis, Physiology (medical), Sarcopenia, medicine, Orthopedics and Sports Medicine, 030304 developmental biology
Abstract

Summary The age-related loss of skeletal muscle mass and function (sarcopenia) is a consistent hallmark of ageing. Apoptosis plays an importantroleinmuscleatrophy,andtheintentofthisstudywasto specify whether apoptosis is restricted to myofibre nuclei (myonuclei)oroccursinsatellitecellsorstromalcellsofextracellularmatrix (ECM). Sarcopenia in mouse gastrocnemius muscle was characterized by myofibre atrophy, oxidative type grouping, delocalization of myonuclei and ECM fibrosis. Terminal deoxynucleotidyl transferase-mediated dUTP nick end-labelling (TUNEL) indicated a sharp rise in apoptosis during ageing. TUNEL coupled with immunostaining for dystrophin, paired box protein-7 (Pax7) or laminin-2a, respectively, was used to identify apoptosis in myonuclei, satellite cells and stromal cells. In adult muscle, apoptosis was not detected inmyofibres,butwasrestrictedtostromalcells.Moreover,theagerelated rise in apoptotic nuclei was essentially due to stromal cells. Myofibre-associatedapoptosisneverthelessoccurredinoldmuscle, but represented < 20% of the total muscle apoptosis. Specifically, apoptosis in old muscle affected a small proportion (0.8%) of the myonuclei, buta large part (46%)of the Pax7 + satellite cells. TUNEL coupled with CD31 immunostaining further attributed stromal apoptosis to capillary endothelial cells. Age-dependent rise in apoptotic capillary endothelial cells was concomitant with altered levelsofkeyangiogenicregulators,perlecanandaperlecandomain V (endorepellin) proteolytic product. Collectively, our results indicate that sarcopenia is associated with apoptosis of satellite cells and impairment of capillary functions, which is likely to contribute to the decline in muscle mass and functionality during ageing.

Published
2014

13. A Proof of Concept to Bridge the Gap between Mass Spectrometry Imaging, Protein Identification and Relative Quantitation: MSI~LC-MS/MS-LF

Author

Michel Hébraud, Frédéric Roche, Thierry Astruc, Christophe Chambon, Cécile Coudy-Gandilhon, Laetitia Théron, Delphine Centeno, Léonard Féasson, Didier Rémond, Jean-Claude Barthélémy, Estelle Pujos-Guillot, Daniel Béchet, Tissus animaux, nutrition, digestion, écosystème et métabolisme (TANDEM), Institut National de la Recherche Agronomique (INRA)-Ecole Nationale Vétérinaire de Toulouse (ENVT), Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-INP. Ecole Nationale Supérieure Agronomique de Toulouse, Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées, Unité de Nutrition Humaine (UNH), Institut National de la Recherche Agronomique (INRA)-Université d'Auvergne - Clermont-Ferrand I (UdA)-Clermont Université, Qualité des Produits Animaux (QuaPA), Institut National de la Recherche Agronomique (INRA), Service de Physiologie Clinique et de l’Exercice, Faculté de Médecine Jacques Lisfranc, Biologie, Ingénierie et Imagerie de la Greffe de Cornée (EA 2521, JE2521, IFR143), Université Jean Monnet [Saint-Étienne] (UJM), Laboratoire Interuniversitaire de Biologie de la Motricité (LIBM ), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Université Jean Monnet [Saint-Étienne] (UJM)-Université Savoie Mont Blanc (USMB [Université de Savoie] [Université de Chambéry]), Microbiologie Equipe Qualité et Sécurité des Aliments (INRA), Unité de Nutrition Humaine - Clermont Auvergne (UNH), Institut National de la Recherche Agronomique (INRA)-Université Clermont Auvergne (UCA), Plateforme d'Exploration du Métabolisme, Université d'Auvergne - Clermont-Ferrand I (UdA)-Clermont Université-Institut National de la Recherche Agronomique (INRA), Université Savoie Mont Blanc (USMB [Université de Savoie] [Université de Chambéry])-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Université Jean Monnet [Saint-Étienne] (UJM), Plateforme Exploration du Métabolisme (PFEM), Institut National de la Recherche Agronomique (INRA)-Université Blaise Pascal - Clermont-Ferrand 2 (UBP)-MetaboHUB-Clermont, MetaboHUB-MetaboHUB, Service de Physiologie Clinique et de l'Exercice [CHU de Saint-Etienne], Centre Hospitalier Universitaire de Saint-Etienne [CHU Saint-Etienne] (CHU ST-E)-Université Jean Monnet - Saint-Étienne (UJM), Biologie, Ingénierie et Imagerie pour l'Ophtalmologie (BIIO), Université Jean Monnet - Saint-Étienne (UJM), Université de Lyon-Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Université Savoie Mont Blanc (USMB [Université de Savoie] [Université de Chambéry]), SECurité des ALIments et Microbiologie, and Institut National de la Recherche Agronomique (INRA)-École nationale d'ingénieurs des techniques des industries agricoles et alimentaires (ENITIAA)-École nationale vétérinaire, agroalimentaire et de l'alimentation Nantes-Atlantique (ONIRIS)

Subjects
0301 basic medicine, [SDV]Life Sciences [q-bio], Clinical Biochemistry, MALDI mass spectrometry imaging, protein identification, label-free quantitation, skeletal muscle, lcsh:QR1-502, Biochemistry, Article, Mass spectrometry imaging, lcsh:Microbiology, Matrix (chemical analysis), 03 medical and health sciences, Structural Biology, spectrométrie de masse, Lc ms ms, Protein purification, Molecular Biology, neoplasms, ComputingMilieux_MISCELLANEOUS, Chromatography, Laser ablation, Chemistry, muscle squelettique, digestive system diseases, quantification, Label-free quantification, 030104 developmental biology, Tissue sections, protéine, identification, Protein identification
Abstract

International audience; Mass spectrometry imaging (MSI) is a powerful tool to visualize the spatial distribution of molecules on a tissue section. The main limitation of MALDI-MSI of proteins is the lack of direct identification. Therefore, this study focuses on a MSI~LC-MS/MS-LF workflow to link the results from MALDI-MSI with potential peak identification and label-free quantitation, using only one tissue section. At first, we studied the impact of matrix deposition and laser ablation on protein extraction from the tissue section. Then, we did a back-correlation of the m/z of the proteins detected by MALDI-MSI to those identified by label-free quantitation. This allowed us to compare the label-free quantitation of proteins obtained in LC-MS/MS with the peak intensities observed in MALDI-MSI. We managed to link identification to nine peaks observed by MALDI-MSI. The results showed that the MSI~LC-MS/MS-LF workflow (i) allowed us to study a representative muscle proteome compared to a classical bottom-up workflow; and (ii) was sparsely impacted by matrix deposition and laser ablation. This workflow, performed as a proof-of-concept, suggests that a single tissue section can be used to perform MALDI-MSI and protein extraction, identification, and relative quantitation.

Published
2016

14. Lower skeletal muscle capillarization in hypertensive elderly men

Author

Frédéric Roche, Léonard Féasson, Bruno Meunier, Daniel Béchet, Daniel Taillandier, Cécile Coudy-Gandilhon, Marine Gueugneau, Lydie Combaret, Cécile Polge, Jean-Claude Barthélémy, Didier Attaix, Unité de Nutrition Humaine (UNH), Institut National de la Recherche Agronomique (INRA)-Université d'Auvergne - Clermont-Ferrand I (UdA)-Clermont Université, Unité Mixte de Recherches sur les Herbivores - UMR 1213 (UMRH), VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Institut National de la Recherche Agronomique (INRA), Service de Physiologie Clinique et de l Exercice, CHU Nord, Faculté de Medecine Jacques Lisfranc, Université Jean Monnet (Saint-Etienne), Centre de Référence des Maladies Neuromusculaires Rares, Unité de Myologie, Centre Hospitalier Universitaire (CHU), Laboratoire de Physiologie de l'Exercice EA4338 (LPE), Université Jean Monnet [Saint-Étienne] (UJM)-Université Savoie Mont Blanc (USMB [Université de Savoie] [Université de Chambéry]), Institut de recherche Expérimentale et Clinique-Pôle d'Endocrinologie, Diabétologie, et Nutrition (EDIN), Université Catholique de Louvain (UCL), Laboratoire Interuniversitaire de Biologie de la Motricité (LIBM ), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Université Jean Monnet [Saint-Étienne] (UJM)-Université Savoie Mont Blanc (USMB [Université de Savoie] [Université de Chambéry]), Fondation Caisse d'Epargne Rhone-Alpes 30, European Union Collaborative Project MyoAge EC-Fp7 CT-223576, Region Auvergne, Fonds Europeens de Developpement Regional (FEDER) 23000422, Unité de Nutrition Humaine ( UNH ), Institut National de la Recherche Agronomique ( INRA ) -Université d'Auvergne - Clermont-Ferrand I ( UdA ) -Clermont Université, Unité Mixte de Recherches sur les Herbivores ( UMR 1213 Herbivores ), VetAgro Sup ( VAS ) -AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Institut National de la Recherche Agronomique ( INRA ), Centre Hospitalier Universitaire ( CHU ), Laboratoire de Physiologie de l'Exercice, Université de Lyon, Université Catholique de Louvain ( UCL ), Université d'Auvergne - Clermont-Ferrand I (UdA)-Clermont Université-Institut National de la Recherche Agronomique (INRA), Unité Mixte de Recherche sur les Herbivores - UMR 1213 (UMRH), VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Institut National de la Recherche Agronomique (INRA)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement, Université Catholique de Louvain = Catholic University of Louvain (UCL), Institut National de la Recherche Agronomique (INRA)-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS), Service de Physiologie Clinique et de l'Exercice [CHU de Saint-Etienne], Centre Hospitalier Universitaire de Saint-Etienne [CHU Saint-Etienne] (CHU ST-E)-Université Jean Monnet - Saint-Étienne (UJM), Laboratoire de Physiologie de l'Exercice (LPE), Université Jean Monnet - Saint-Étienne (UJM), and Université de Lyon-Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Université Savoie Mont Blanc (USMB [Université de Savoie] [Université de Chambéry])

Subjects
Male, Biopsy, [ SDV.AEN ] Life Sciences [q-bio]/Food and Nutrition, Muscle Fibers, Skeletal, 030204 cardiovascular system & hematology, Biochemistry, capillary, Extracellular matrix, 0302 clinical medicine, Endocrinology, Fibrosis, medicine.diagnostic_test, [SDV.MHEP.GEG]Life Sciences [q-bio]/Human health and pathology/Geriatry and gerontology, Age Factors, muscle fiber, Extracellular Matrix, medicine.anatomical_structure, Lower Extremity, medicine.medical_specialty, hypertension, Neovascularization, Physiologic, [ SDV.MHEP.GEG ] Life Sciences [q-bio]/Human health and pathology/Geriatry and gerontology, metabolic syndrome, Electron Transport Complex IV, sarcopenia, 03 medical and health sciences, Young Adult, Sex Factors, Internal medicine, Genetics, medicine, Humans, Risk factor, Muscle, Skeletal, Molecular Biology, Aged, business.industry, aging, Skeletal muscle, Cell Biology, medicine.disease, Endomysium, Capillaries, Sarcopenia, Metabolic syndrome, business, [SDV.AEN]Life Sciences [q-bio]/Food and Nutrition, 030217 neurology & neurosurgery
Abstract

The authors wish to gratefully acknowledge Professor Philippe Courpron for his central role in initiating this work. The authors are grateful to the Fondation pour l'Université de Lyon for assistance with obtaining reagents; Aging strongly affects the skeletal muscle and is associated with microvascular dysfunctions. Age is also a primary risk factor for the metabolic syndrome, which is a cluster of metabolic and cardiovascular symptoms. Among the metabolic syndrome components, hypertension is the most prevalent in elderly subjects and has a central role in vascular alterations. Despite critical clinical outcomes, the effects of hypertension and metabolic syndrome on skeletal muscle capillarization have poorly been investigated during aging. In the present study, muscle biopsies from normotensive young (YO) and elderly (ELc) men, and elderly men with hypertension (EL-HT) or metabolic syndrome (EL-MS) were assessed for the number of capillaries around a fiber (CAF), capillary-to-fiber perimeter exchange (CFPE), length of contact to perimeter of fiber ratio (LC/PF), capillary tortuosity, and for extracellular matrix (ECM) embedding capillaries. As capillarization and muscle mitochondrial oxidative capacity may be associated, we also investigated cytochrome c oxidase (COX) content. Our findings indicate that capillarization and COX did not change between normotensive adult and old individuals. They further reveal that hypertension in elderly men is associated with reduced CAF (ELc: 5.2 +/- 0.4, EL-HT: 4.1 +/- 0.2, P < 0.02 for type I fibers; ELc: 4.1 +/- 0.2, EL-HT: 3.1 +/- 0.3, P < 0.03 for type IIA fibers), CFPE (ELc: 7.9 +/- 0.7, EL-HT: 6.4 +/- 0.4 capillaries/1000 mu m, P < 0.03 for type I fibers; ELc: 6.5 +/- 0.4, EL-HT: 5.2 +/- 0.4 capillaries/1000 mu m, P < 0.03 for type IIA fibers), LC/PF (ELc: 23.3 +/- 1.2, EL-HT: 17.8 +/- 0.6%, P < 0.01 for type I fibers; ELc: 19.8 +/- 1.1, EL-HT: 15.6 +/- 0.8%, P < 0.01 for type IIA fibers) and capillary tortuosity, and with ECM endomysium fibrosis. Capillary rarefaction also correlated with lower COX content in the old hypertensive muscle. No further modification occurred with metabolic syndrome in elderly men. Collectively, our results suggest that hypertension plays a central role in muscle capillarization during aging, and that the other components of metabolic syndrome do not make major additional changes in the aged skeletal muscle capillary network

Published
2016

15. Skeletal muscle lipid content and oxidative activity in relation to muscle fiber type in aging and metabolic syndrome

Author

Cécile Polge, Daniel Béchet, Léonard Féasson, Daniel Taillandier, Frédéric Roche, Bruno Meunier, Brigitte Picard, Lydie Combaret, Didier Attaix, Cécile Coudy-Gandilhon, Jean-Claude Barthélémy, Christiane Barboiron, Julien Verney, Laetitia Théron, Marine Gueugneau, Unité de Nutrition Humaine - Clermont Auvergne (UNH), Institut National de la Recherche Agronomique (INRA)-Université Clermont Auvergne (UCA), Centre de Recherche en Nutrition Humaine, Unité Mixte de Recherches sur les Herbivores - UMR 1213 (UMRH), VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Institut National de la Recherche Agronomique (INRA), VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS), Centre Référent Maladies Neuromusculaires Rares Rhône-Alpes, Unité de Myologie, Centre Hospitalier Universitaire de Saint-Etienne (CHU de Saint-Etienne), Laboratoire de Physiologie de l'Exercice EA4338 (LPE), Université Jean Monnet [Saint-Étienne] (UJM)-Université Savoie Mont Blanc (USMB [Université de Savoie] [Université de Chambéry]), Université de Lyon, Hôpital Nord - Faculté de MédecineJacques Lisfranc, Service de Physiologie Clinique et de l'Exercice, PRES Université de Lyon, Université Jean Monnet (Saint-Etienne), Hôpital Nord - Faculté de Médecine Jacques Lisfranc, Service de Physiologie Clinique et de l'Exercice, Unité de Nutrition Humaine (UNH), Université d'Auvergne - Clermont-Ferrand I (UdA)-Clermont Université-Institut National de la Recherche Agronomique (INRA), Unité Mixte de Recherche sur les Herbivores - UMR 1213 (UMRH), Institut National de la Recherche Agronomique (INRA)-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement, Institut National de la Recherche Agronomique (INRA)-Université d'Auvergne - Clermont-Ferrand I (UdA)-Clermont Université, VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Institut National de la Recherche Agronomique (INRA)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement, Unité de Nutrition Humaine - Clermont Auvergne ( UNH ), Université Clermont Auvergne ( UCA ) -Institut national de la recherche agronomique [Auvergne/Rhône-Alpes] ( INRA Auvergne/Rhône-Alpes ), Unité Mixte de Recherches sur les Herbivores ( UMR 1213 Herbivores ), VetAgro Sup ( VAS ) -AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Institut National de la Recherche Agronomique ( INRA ), Institut d'Enseignement Supérieur et de Recherche en Alimentation, Santé Animale, Sciences Agronomiques et de l'Environnement, Centre Hospitalier Universitaire de Saint-Etienne ( CHU de Saint-Etienne ), Laboratoire de Physiologie de l'Exercice EA4338, Université de Lyon (COMUE), Institut National de la Recherche Agronomique (INRA)-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS), Centre Hospitalier Universitaire de Saint-Etienne [CHU Saint-Etienne] (CHU ST-E), Laboratoire de Physiologie de l'Exercice (LPE), Université Jean Monnet - Saint-Étienne (UJM), Service de Physiologie Clinique et de l'Exercice [CHU de Saint-Etienne], and Centre Hospitalier Universitaire de Saint-Etienne [CHU Saint-Etienne] (CHU ST-E)-Université Jean Monnet - Saint-Étienne (UJM)

Subjects
Male, Sarcopenia, medicine.medical_specialty, masse musculaire, [ SDV.AEN ] Life Sciences [q-bio]/Food and Nutrition, Biopsy, lipid droplets, Muscle Fibers, Skeletal, metabolic syndrome, Electron Transport Complex IV, Young Adult, Absorptiometry, Photon, Atrophy, Internal medicine, Lipid droplet, Humans, Medicine, Cytochrome c oxidase, Muscle Strength, Intramyocellular lipids, skeletal muscle, Aged, syndrome métabolique, biology, business.industry, aging, fiber types, Skeletal muscle, metabolic x syndrome, vieillissement, Lipid Metabolism, medicine.disease, Endocrinology, medicine.anatomical_structure, muscle mass, Ageing, ageing, Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization, Body Composition, biology.protein, teneur en lipides, oil content, Geriatrics and Gerontology, Metabolic syndrome, Energy Metabolism, business, [SDV.AEN]Life Sciences [q-bio]/Food and Nutrition
Abstract

One of the most noticeable effects of aging is the reduction in skeletal muscle mass and strength (sarcopenia). The metabolic syndrome (MS) is also prevalent in old subjects, but its relevance to skeletal muscle characteristics has poorly been investigated. Immunohistochemical studies were performed with muscle biopsies from young (22 years) and old (73 years) men with and without MS to reveal age-dependent and MS-associated modifications of fiber-type characteristics. Atrophy of type II fibers and altered fiber shape characterized muscle aging in lean healthy men. In contrast, increased cross-sectional area of the most abundant type I and type IIA fibers, and reduced cytochrome c oxidase content in all fiber types, characterized MS. Aging and particularly MS were associated with accumulation of intramyocellular lipid droplets. Although lipids mostly accumulated in type I fibers, matrix-assisted laser desorption/ionization–mass spectrometry imaging of intramyocellular lipids did not distinguish fiber types, but clearly separated young, old, and MS subjects. In conclusion, our study suggests that MS in the elderly persons is associated with alterations in skeletal muscle at a fiber-type specific level. Overall, these fiber type-specific modifications may be important both for the age-related loss of muscle mass and strength and for the increased prevalence of MS in elderly subjects.

Published
2015

16. Proteomics of muscle chronological ageing in post-menopausal women

Author

Cécile Polge, Gillian Butler-Browne, Lydie Combaret, Christophe Chambon, Cécile Coudy-Gandilhon, Daniel Taillandier, Marine Gueugneau, Daniel Béchet, Ophélie Gourbeyre, Andrea B. Maier, Didier Attaix, Bertrand Friguet, Vieillissement Cellulaire Intégré et Inflammation (VCII), Adaptation Biologique et Vieillissement = Biological Adaptation and Ageing (B2A), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut de Biologie Paris Seine (IBPS), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut de Biologie Paris Seine (IBPS), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), European Union Collaborative Project MyoAge [EC Fp7 CT-223576], Fondation Caisse d'Epargne Rhone-Alpes (CERA Sarcopenie) [30], Region Auvergne, Fonds Europeens de Developpement Regional (FEDER) [23000422], FEDER [35380 T2a 2011 Prenusa], European Project: 223576,EC:FP7:HEALTH,FP7-HEALTH-2007-B,MYOAGE(2009), Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut de Biologie Paris Seine (IBPS), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut de Biologie Paris Seine (IBPS), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Béchet, Daniel, Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut de Biologie Paris Seine (IBPS), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Internal medicine, MOVE Research Institute, and UCL - SSS/IREC/EDIN - Pôle d'endocrinologie, diabète et nutrition

Subjects
Proteomics, Sarcopenia, Aging, Cytoplasm, Skeletal muscle, Sarcomere, Myosin, protéome, Cytotoxins, Muscles, muscle squelettique, Blood Proteins, Middle Aged, Muscle atrophy, atrophie musculaire, Cell biology, Mitochondria, Postmenopause, medicine.anatomical_structure, Alimentation et Nutrition, femme menopausée, Female, medicine.symptom, biomarqueur, Biotechnology, Muscle contraction, Research Article, Human, Signal Transduction, Sarcomeres, Ageing, Biomarkers, [SDV.BC]Life Sciences [q-bio]/Cellular Biology, Biology, sarcopenie, Genetics, medicine, Food and Nutrition, Humans, Muscle, Skeletal, Aged, Lipid Metabolism, Electrophoreses, Cytoskeletal Proteins, Oxidative Stress, Proteostasis, Proteolysis, Myofibril, Energy Metabolism, Transcriptome
Abstract

International audience; Background: Muscle ageing contributes to both loss of functional autonomy and increased morbidity. Muscle atrophy accelerates after 50 years of age, but the mechanisms involved are complex and likely result from the alteration of a variety of interrelated functions. In order to better understand the molecular mechanisms underlying muscle chronological ageing in human, we have undertaken a top-down differential proteomic approach to identify novel biomarkers after the fifth decade of age. Results: Muscle samples were compared between adult (56 years) and old (78 years) post-menopausal women. In addition to total muscle extracts, low-ionic strength extracts were investigated to remove high abundance myofibrillar proteins and improve the detection of low abundance proteins. Two-dimensional gel electrophoreses with overlapping IPGs were used to improve the separation of muscle proteins. Overall, 1919 protein spots were matched between all individuals, 95 were differentially expressed and identified by mass spectrometry, and they corresponded to 67 different proteins. Our results suggested important modifications in cytosolic, mitochondrial and lipid energy metabolism, which may relate to dysfunctions in old muscle force generation. A fraction of the differentially expressed proteins were linked to the sarcomere and cytoskeleton (myosin light-chains, troponin T, ankyrin repeat domain-containing protein-2, vinculin, four and a half LIM domain protein-3), which may account for alterations in contractile properties. In line with muscle contraction, we also identified proteins related to calcium signal transduction (calsequestrin-1, sarcalumenin, myozenin-1, annexins). Muscle ageing was further characterized by the differential regulation of several proteins implicated in cytoprotection (catalase, peroxiredoxins), ion homeostasis (carbonic anhydrases, selenium-binding protein 1) and detoxification (aldo-keto reductases, aldehyde dehydrogenases). Notably, many of the differentially expressed proteins were central for proteostasis, including heat shock proteins and proteins involved in proteolysis (valosin-containing protein, proteasome subunit beta type-4, mitochondrial elongation factor-Tu). Conclusions: This study describes the most extensive proteomic analysis of muscle ageing in humans, and identified 34 new potential biomarkers. None of them were previously recognized as differentially expressed in old muscles, and each may represent a novel starting point to elucidate the mechanisms of muscle chronological ageing in humans.

Published
2014

17. Apoptosis in capillary endothelial cells in ageing skeletal muscle

Author

Claire Lethias, Cécile Coudy-Gandilhon, Daniel Béchet, Kijoon Lee, Lydie Combaret, Anne Listrat, Didier Attaix, Huijuan Wang, Bruno Meunier, Cécile Polge, Marine Gueugneau, Kheng Lim Goh, Daniel Taillandier, Unité de Nutrition Humaine (UNH), Université d'Auvergne - Clermont-Ferrand I (UdA)-Clermont Université-Institut National de la Recherche Agronomique (INRA), Unité Mixte de Recherche sur les Herbivores - UMR 1213 (UMRH), Institut National de la Recherche Agronomique (INRA)-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement, Laboratoire de Biologie Tissulaire et d'ingénierie Thérapeutique UMR 5305 (LBTI), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS), School of Chemical and Biomedical Engineering, Nanyang Technological University [Singapour], School of Mechanical and Systems Engineering, Newcastle University International Singapore (NUIS), NTU Academic Research Fund (AcRF) Tier 1 [RG37/07], Egide Merlion [5.03.07], European Commission MyoAge [EC Fp7 CT-223756], Fondation Caisse d'Epargne Rhone Alpes (CERA), Fondation Rhone Alpes Futur, NTU, Conseil Regional Auvergne, Fonds Europeens de Developpement Regional (FEDER), Institut National de la Recherche Agronomique (INRA)-Université d'Auvergne - Clermont-Ferrand I (UdA)-Clermont Université, VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Institut National de la Recherche Agronomique (INRA)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement, Unité Mixte de Recherches sur les Herbivores - UMR 1213 (UMRH), VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Institut National de la Recherche Agronomique (INRA), Institut National de la Recherche Agronomique (INRA)-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS), Unité de Nutrition Humaine ( UNH ), Clermont Université-Université d'Auvergne - Clermont-Ferrand I ( UdA ) -Institut National de la Recherche Agronomique ( INRA ), Unité Mixte de Recherches sur les Herbivores ( UMR 1213 Herbivores ), VetAgro Sup ( VAS ) -AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Institut National de la Recherche Agronomique ( INRA ), Laboratoire de Biologie Tissulaire et d'ingénierie Thérapeutique UMR 5305 ( LBTI ), Université Claude Bernard Lyon 1 ( UCBL ), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique ( CNRS ), Newcastle University International Singapore ( NUIS ), and Béchet, Daniel

Subjects
Male, Pathology, Aging, satellite stem cell, Angiogenesis, Muscle Fibers, Skeletal, souris, [ SDV.BA ] Life Sciences [q-bio]/Animal biology, angiogenesis, 0302 clinical medicine, Animal biology, 0303 health sciences, TUNEL assay, [SDV.BA]Life Sciences [q-bio]/Animal biology, digestive, oral, and skin physiology, apoptosis, Tenascin, vieillissement, musculoskeletal system, Cell biology, atrophie musculaire, medicine.anatomical_structure, muscle mass, muscular atrophy, dystrophine, hormones, hormone substitutes, and hormone antagonists, medicine.medical_specialty, Stromal cell, mice, Satellite Cells, Skeletal Muscle, myofibre, masse musculaire, activité anti apoptotique, matrice extracellulaire, Médecine humaine et pathologie, Biology, sarcopenia, 03 medical and health sciences, Gastrocnemius muscle, Atrophy, sarcopenie, cellule satellite, [ SDV.MHEP ] Life Sciences [q-bio]/Human health and pathology, Biologie animale, fonctionnement, medicine, Animals, Muscle, Skeletal, 030304 developmental biology, Cell Nucleus, cellule stromale, Engineering::Bioengineering [DRNTU], Skeletal muscle, Endothelial Cells, Cell Biology, Original Articles, medicine.disease, Mice, Inbred C57BL, Apoptosis, ageing, Sarcopenia, Human health and pathology, Stromal Cells, Extracellular Space, cellule endotheliale, 030217 neurology & neurosurgery, Heparan Sulfate Proteoglycans, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology, squelette
Abstract

International audience; The age-related loss of skeletal muscle mass and function (sarcopenia) is a consistent hallmark of ageing. Apoptosis plays an important role in muscle atrophy, and the intent of this study was to specify whether apoptosis is restricted to myofibre nuclei (myonuclei) or occurs in satellite cells or stromal cells of extracellular matrix (ECM). Sarcopenia in mouse gastrocnemius muscle was characterized by myofibre atrophy, oxidative type grouping, delocalization of myonuclei and ECM fibrosis. Terminal deoxynucleotidyl transferase-mediated dUTP nick end-labelling (TUNEL) indicated a sharp rise in apoptosis during ageing. TUNEL coupled with immunostaining for dystrophin, paired box protein-7 (Pax7) or laminin-2α, respectively, was used to identify apoptosis in myonuclei, satellite cells and stromal cells. In adult muscle, apoptosis was not detected in myofibres, but was restricted to stromal cells. Moreover, the age-related rise in apoptotic nuclei was essentially due to stromal cells. Myofibre-associated apoptosis nevertheless occurred in old muscle, but represented < 20% of the total muscle apoptosis. Specifically, apoptosis in old muscle affected a small proportion (0.8%) of the myonuclei, but a large part (46%) of the Pax7(+) satellite cells. TUNEL coupled with CD31 immunostaining further attributed stromal apoptosis to capillary endothelial cells. Age-dependent rise in apoptotic capillary endothelial cells was concomitant with altered levels of key angiogenic regulators, perlecan and a perlecan domain V (endorepellin) proteolytic product. Collectively, our results indicate that sarcopenia is associated with apoptosis of satellite cells and impairment of capillary functions, which is likely to contribute to the decline in muscle mass and functionality during ageing.

Published
2013

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