Signalling pathways regulating muscle mass in ageing skeletal muscle
| العنوان: | Signalling pathways regulating muscle mass in ageing skeletal muscle |
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| المؤلفون: | Luana Toniolo, L. Barberi, Astrid Y. Bijlsma, Antonio L. Serrano, Carel G. M. Meskers, Lars Larsson, Mario Pende, Rosario Rizzuto, Marco Sandri, Kenneth A. Dyar, Cristina Mammucari, Andrea B. Maier, Giorgia Pallafacchina, M. Roceri, Pura Muñoz-Cánoves, Stefano Schiaffino, Antonio Paoli, D. Pion, Giulia Milan, Bert Blaauw, Antonio Musarò, Carlo Reggiani, Vanina Romanello |
| المساهمون: | Faculty of Behavioural and Movement Sciences, Neuromechanics, AMS - Ageing and Morbidity, Dulbecco Telethon Institute, Venetian Institute Molecular Medicine (VIMM), CNR Institute of Neuroscience, National Research Council [Italy] (CNR), Department of Biomedical Sciences, Universita degli Studi di Padova, Department of Anatomy, Histology, Forensic Medicine and Orthopedic [Roma] (DAHFMO), Institut Pasteur, Fondation Cenci Bolognetti - Istituto Pasteur Italia, Fondazione Cenci Bolognetti, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP)-Università degli Studi di Roma 'La Sapienza' = Sapienza University [Rome], Department of internal Medicine, University of Amsterdam [Amsterdam] (UvA), Department of Gerontology and Geriatrics, Leiden University Medical Center (LUMC), Department of Rehabilitation, Centre de recherche Croissance et signalisation (UMR_S 845), Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Descartes - Paris 5 (UPD5), ICREA Infection Biology Laboratory (Department of Experimental and Health Sciences), Universitat Pompeu Fabra [Barcelona] (UPF), Department of Biobehavioral Health, Pennsylvania State University (Penn State), Penn State System-Penn State System, Department of Neuroscience, Clinical Neurophysiology, Uppsala University, Supported by the EC FP7 Project MYOAGE (to LL, ABM, PM-C, AM, MP, CR, MS, and SS), Fondation Thierry Latran, MIUR and AFM (to AM), the Swedish Research Council (8651 to LL), MDA, Ministerio de Ciencia e Innovacion of Spain SAF2012-38547, FIS-PS09/01267, PLE2009-0124, Marató/TV3 and AFM (to PM-C and ALS), EU interregio project PANGEA (to CR), King Gustaf V and Queen Victoria’s Foundation, and the National Institute of Health Grants (AG-14731, AR-45627 and AR-47318 to LL)., European Project: 223576,EC:FP7:HEALTH,FP7-HEALTH-2007-B,MYOAGE(2009), Università degli Studi di Padova = University of Padua (Unipd), Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP)-Università degli Studi di Roma 'La Sapienza' = Sapienza University [Rome] (UNIROMA), Universiteit Leiden-Universiteit Leiden, Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), MOVE Research Institute, Internal medicine, Venetian Institute of Molecular Medicine, Padua, Department of Anatomy, Histology, Forensic Medicine and Orthopedic, Università degli Studi di Roma 'La Sapienza' [Rome]-Réseau International des Instituts Pasteur (RIIP)-Institut Pasteur, Fondation Cenci Bolognetti - Istituto Pasteur Italia, Fondazione Cenci Bolognetti, Réseau International des Instituts Pasteur (RIIP), Venetian Institute of Molecular Medicine, Padova, Italy, Universitat Pompeu Fabra [Barcelona] |
| المصدر: | Biogerontology, 14(3), 303-23. Springer Netherlands Biogerontology Biogerontology, Springer Verlag, 2013, 14 (3), pp.303-23. ⟨10.1007/s10522-013-9432-9⟩ Biogerontology; Vol 14 Sandri, M, Barberi, L, Bijlsma, A Y, Blaauw, B, Dyar, K A, Milan, G, Mammucari, C, Meskers, C G M, Pallafacchina, G, Paoli, A, Pion, D, Roceri, M, Romanello, V, Serrano, A L, Toniolo, L, Larsson, L, Maier, A B, Munoz-Canoves, P, Musaro, A, Pende, M, Reggiani, C, Rizzuto, R & Schiaffino, S 2013, ' Signalling pathways regulating muscle mass in ageing skeletal muscle. The role of the IGF1-Akt-mTOR-FoxO pathway ', Biogerontology, vol. 14, no. 3, pp. 303-323 . https://doi.org/10.1007/s10522-013-9432-9Test Biogerontology, 2013, 14 (3), pp.303-23. ⟨10.1007/s10522-013-9432-9⟩ Biogerontology, 14(3), 303-323. Springer Netherlands Biogerontology, 14(3), 303-323 Sandri, M, Barberi, L, Bijlsma, A Y, Blaauw, B, Dyar, K A, Milan, G, Mammucari, C, Meskers, C G M, Pallafacchina, G, Paoli, A, Pion, D, Roceri, M, Romanello, V, Serrano, A L, Toniolo, L, Larsson, L, Maier, A B, Muñoz-Cánoves, P, Musarò, A, Pende, M, Reggiani, C, Rizzuto, R & Schiaffino, S 2013, ' Signalling pathways regulating muscle mass in ageing skeletal muscle : the role of the IGF1-Akt-mTOR-FoxO pathway ', Biogerontology, vol. 14, no. 3, pp. 303-23 . https://doi.org/10.1007/s10522-013-9432-9Test |
| سنة النشر: | 2013 |
| مصطلحات موضوعية: | Male, Sarcopenia, FOXO1, mTORC1, Transgenic, Muscle hypertrophy, Sarcopenia/physiopathology, MESH: Serpin E2, Mice, SKP Cullin F-Box Protein Ligases/genetics, 0302 clinical medicine, Models, Serpin E2, 80 and over, MESH: Aging, MESH: Animals, MESH: Sarcopenia, Aged, 80 and over, Muscle Proteins/genetics, 0303 health sciences, Insulin-Like Growth Factor I/physiology, TOR Serine-Threonine Kinases, IGF1, Forkhead Transcription Factors/physiology, MESH: Young Adult, Mice, Inbred DBA, MESH: SKP Cullin F-Box Protein Ligases, medicine.medical_specialty, Knockout, muscle atrophy, signaling, aging, IGF-1, 03 medical and health sciences, MESH: Muscle Proteins, SDG 3 - Good Health and Well-being, MESH: Forkhead Transcription Factors, Skeletal/physiology, Serpin E2/genetics, Humans, Inbred DBA, Ubiquitin-Protein Ligases/genetics, Protein kinase B, Aged, MESH: Adolescent, MESH: Humans, MESH: Mice, Inbred DBA, MESH: Proto-Oncogene Proteins c-akt, Animal, MESH: Adult, medicine.disease, MESH: Ubiquitin-Protein Ligases, Mice, Inbred C57BL, Muscle, Skeletal/physiology, Ageing, MESH: Microtubule-Associated Proteins, Endocrinology, TOR Serine-Threonine Kinases/physiology, FoxO, Geriatrics and Gerontology, Gerontology, MESH: Female, 030217 neurology & neurosurgery, MESH: Signal Transduction, MESH: Insulin-Like Growth Factor I, Muscle Proteins, Inbred C57BL, MESH: Mice, Knockout, Autophagy-Related Protein 7, Tripartite Motif Proteins, MESH: Aged, 80 and over, Insulin-Like Growth Factor I, MESH: Aged, Mice, Knockout, MESH: Muscle, Skeletal, Forkhead Box Protein O1, Forkhead Transcription Factors, medicine.anatomical_structure, MESH: Models, Animal, Models, Animal, mTOR, Muscle, Female, Microtubule-Associated Proteins, Signal Transduction, Adult, Adolescent, MESH: Mice, Transgenic, Ubiquitin-Protein Ligases, Mice, Transgenic, Protein degradation, Biology, Young Adult, MESH: Mice, Inbred C57BL, Internal medicine, medicine, Animals, [SDV.BBM]Life Sciences [q-bio]/Biochemistry, Molecular Biology, Muscle, Skeletal, MESH: Mice, PI3K/AKT/mTOR pathway, MESH: TOR Serine-Threonine Kinases, 030304 developmental biology, SKP Cullin F-Box Protein Ligases, Signal Transduction/physiology, Akt, Skeletal muscle, Proto-Oncogene Proteins c-akt/physiology, Microtubule-Associated Proteins/genetics, MESH: Male, Aging/physiology, Proto-Oncogene Proteins c-akt |
| الوصف: | International audience; During ageing skeletal muscles undergo a process of structural and functional remodelling that leads to sarcopenia, a syndrome characterized by loss of muscle mass and force and a major cause of physical frailty. To determine the causes of sarcopenia and identify potential targets for interventions aimed at mitigating ageing-dependent muscle wasting, we focussed on the main signalling pathway known to control protein turnover in skeletal muscle, consisting of the insulin-like growth factor 1 (IGF1), the kinase Akt and its downstream effectors, the mammalian target of rapamycin (mTOR) and the transcription factor FoxO. Expression analyses at the transcript and protein level, carried out on well-characterized cohorts of young, old sedentary and old active individuals and on mice aged 200, 500 and 800 days, revealed only modest age-related differences in this pathway. Our findings suggest that during ageing there is no downregulation of IGF1/Akt pathway and that sarcopenia is not due to FoxO activation and upregulation of the proteolytic systems. A potentially interesting result was the increased phosphorylation of the ribosomal protein S6, indicative of increased activation of mTOR complex1 (mTORC1), in aged mice. This result may provide the rationale why rapamycin treatment and caloric restriction promote longevity, since both interventions blunt activation of mTORC1; however, this change was not statistically significant in humans. Finally, genetic perturbation of these pathways in old mice aimed at promoting muscle hypertrophy via Akt overexpression or preventing muscle loss through inactivation of the ubiquitin ligase atrogin1 were found to paradoxically cause muscle pathology and reduce lifespan, suggesting that drastic activation of the IGF1-Akt pathway may be counterproductive, and that sarcopenia is accelerated, not delayed, when protein degradation pathways are impaired. |
| اللغة: | English |
| تدمد: | 1389-5729 1573-6768 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::14f4a5d65f36ee74ba4de2ecd531c858Test https://hdl.handle.net/1871.1/c3edf814-3c90-4667-8713-c3a120aff07aTest |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....14f4a5d65f36ee74ba4de2ecd531c858 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 13895729 15736768 |
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