Alterations in the in vitro and in vivo regulation of muscle regeneration in healthy ageing and the influence of sarcopenia
Abstract Background Sarcopenia is defined as the age‐related loss of skeletal muscle mass and function. While all humans lose muscle with age, 2–5% of elderly adults develop functional consequences (disabilities). The aim of this study was to investigate muscle myogenesis in healthy elderly adults,...
| Main Authors: | , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Wiley
2018-02-01
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| Series: | Journal of Cachexia, Sarcopenia and Muscle |
| Subjects: | |
| Online Access: | https://doi.org/10.1002/jcsm.12252 |
| _version_ | 1797203526245416960 |
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| author | Joanna Brzeszczyńska Angelika Meyer Robin McGregor Alain Schilb Simone Degen Valentina Tadini Neil Johns Ramon Langen Annemie Schols David J. Glass Ronenn Roubenoff James A. Ross Kenneth C.H. Fearon Carolyn A. Greig Carsten Jacobi |
| author_facet | Joanna Brzeszczyńska Angelika Meyer Robin McGregor Alain Schilb Simone Degen Valentina Tadini Neil Johns Ramon Langen Annemie Schols David J. Glass Ronenn Roubenoff James A. Ross Kenneth C.H. Fearon Carolyn A. Greig Carsten Jacobi |
| author_sort | Joanna Brzeszczyńska |
| collection | DOAJ |
| description | Abstract Background Sarcopenia is defined as the age‐related loss of skeletal muscle mass and function. While all humans lose muscle with age, 2–5% of elderly adults develop functional consequences (disabilities). The aim of this study was to investigate muscle myogenesis in healthy elderly adults, with or without sarcopenia, compared with middle‐aged controls using both in vivo and in vitro approaches to explore potential biomarker or causative molecular pathways associated with sarcopenic versus non‐sarcopenic skeletal muscle phenotypes during ageing. Methods Biomarkers of multiple molecular pathways associated with muscle regeneration were analysed using quantitative polymerase chain reaction in quadriceps muscle samples obtained from healthy elderly sarcopenic (HSE, n = 7) or non‐sarcopenic (HENS, n = 21) and healthy middle‐aged control (HMC, n = 22) groups. An in vitro system of myogenesis (using myoblasts from human donors aged 17–83 years) was used to mimic the environmental challenges of muscle regeneration over time. Results The muscle biopsies showed evidence of satellite cell activation in HENS (Pax3, P < 0.01, Pax7, P < 0.0001) compared with HMC. Early myogenesis markers Myogenic Differentiation 1 (MyoD1) and Myogenic factor 5 (Myf5) (P < 0.0001) and the late myogenesis marker myogenin (MyoG) (P < 0.01) were increased in HENS. In addition, there was a 30‐fold upregulation of TNF‐α in HENS compared with HMC (P < 0.0001). The in vitro system demonstrated age‐related upregulation of pro‐inflammatory cytokines (2‐fold upregulation of interleukin (IL)‐6, IL‐8 mRNA, increased secretion of tumor necrosis factor‐α (TNF‐α) and IL‐6, all P < 0.05) associated with impaired kinetics of myotube differentiation. The HSE biopsy samples showed satellite cell activation (Pax7, P < 0.05) compared with HMC. However, no significant upregulation of the early myogenesis (MyoD and Myf5) markers was evident; only the late myogenesis marker myogenin was upregulated (P < 0.05). Higher activation of the oxidative stress pathway was found in HENS compared with the HSE group. In contrast, there was 10‐fold higher upregulation of HSPA1A a stress‐induced chaperone acting upon misfolded proteins in HSE compared with the HENS group. Conclusions Both pathological and adaptive processes are active in skeletal muscle during healthy ageing. Muscle regeneration pathways are activated during healthy ageing, but there is evidence of dysregulation in sarcopenia. In addition, increased cellular stress, with an impaired oxidative‐stress and mis‐folded protein response (HSPA1A), may be associated with the development of sarcopenia. The in vitro system of young and old myoblasts replicated some of the differences between young and old muscle. |
| first_indexed | 2024-04-24T08:20:44Z |
| format | Article |
| id | doaj.art-c09f7a587c5642489648c9ba03775860 |
| institution | Directory Open Access Journal |
| issn | 2190-5991 2190-6009 |
| language | English |
| last_indexed | 2024-04-24T08:20:44Z |
| publishDate | 2018-02-01 |
| publisher | Wiley |
| record_format | Article |
| series | Journal of Cachexia, Sarcopenia and Muscle |
| spelling | doaj.art-c09f7a587c5642489648c9ba037758602024-04-17T01:39:25ZengWileyJournal of Cachexia, Sarcopenia and Muscle2190-59912190-60092018-02-01919310510.1002/jcsm.12252Alterations in the in vitro and in vivo regulation of muscle regeneration in healthy ageing and the influence of sarcopeniaJoanna Brzeszczyńska0Angelika Meyer1Robin McGregor2Alain Schilb3Simone Degen4Valentina Tadini5Neil Johns6Ramon Langen7Annemie Schols8David J. Glass9Ronenn Roubenoff10James A. Ross11Kenneth C.H. Fearon12Carolyn A. Greig13Carsten Jacobi14Tissue Injury and Repair Group, Centre for Regenerative Medicine University of Edinburgh Edinburgh UKNovartis Institutes for Biomedical Research Basel, Novartis Pharma AG, CH‐4056 Basel Switzerland and Novartis Institutes for Biomedical Research Cambridge MA USACardiovascular and Metabolic Disease Center, College of Medicine Inje University Busan Republic of KoreaNovartis Institutes for Biomedical Research Basel, Novartis Pharma AG, CH‐4056 Basel Switzerland and Novartis Institutes for Biomedical Research Cambridge MA USANovartis Institutes for Biomedical Research Basel, Novartis Pharma AG, CH‐4056 Basel Switzerland and Novartis Institutes for Biomedical Research Cambridge MA USANovartis Institutes for Biomedical Research Basel, Novartis Pharma AG, CH‐4056 Basel Switzerland and Novartis Institutes for Biomedical Research Cambridge MA USATissue Injury and Repair Group, Centre for Regenerative Medicine University of Edinburgh Edinburgh UKNUTRIM School of Nutrition and Translational Research in Metabolism Maastricht University Maastricht NetherlandsNUTRIM School of Nutrition and Translational Research in Metabolism Maastricht University Maastricht NetherlandsNovartis Institutes for Biomedical Research Basel, Novartis Pharma AG, CH‐4056 Basel Switzerland and Novartis Institutes for Biomedical Research Cambridge MA USANovartis Institutes for Biomedical Research Basel, Novartis Pharma AG, CH‐4056 Basel Switzerland and Novartis Institutes for Biomedical Research Cambridge MA USATissue Injury and Repair Group, Centre for Regenerative Medicine University of Edinburgh Edinburgh UKClinical Sciences (Surgery) University of Edinburgh Edinburgh UKSchool of Sport, Exercise and Rehabilitation Sciences and MRC‐Arthritis Research UK Centre for Musculoskeletal Ageing Research University of Birmingham Birmingham UKNovartis Institutes for Biomedical Research Basel, Novartis Pharma AG, CH‐4056 Basel Switzerland and Novartis Institutes for Biomedical Research Cambridge MA USAAbstract Background Sarcopenia is defined as the age‐related loss of skeletal muscle mass and function. While all humans lose muscle with age, 2–5% of elderly adults develop functional consequences (disabilities). The aim of this study was to investigate muscle myogenesis in healthy elderly adults, with or without sarcopenia, compared with middle‐aged controls using both in vivo and in vitro approaches to explore potential biomarker or causative molecular pathways associated with sarcopenic versus non‐sarcopenic skeletal muscle phenotypes during ageing. Methods Biomarkers of multiple molecular pathways associated with muscle regeneration were analysed using quantitative polymerase chain reaction in quadriceps muscle samples obtained from healthy elderly sarcopenic (HSE, n = 7) or non‐sarcopenic (HENS, n = 21) and healthy middle‐aged control (HMC, n = 22) groups. An in vitro system of myogenesis (using myoblasts from human donors aged 17–83 years) was used to mimic the environmental challenges of muscle regeneration over time. Results The muscle biopsies showed evidence of satellite cell activation in HENS (Pax3, P < 0.01, Pax7, P < 0.0001) compared with HMC. Early myogenesis markers Myogenic Differentiation 1 (MyoD1) and Myogenic factor 5 (Myf5) (P < 0.0001) and the late myogenesis marker myogenin (MyoG) (P < 0.01) were increased in HENS. In addition, there was a 30‐fold upregulation of TNF‐α in HENS compared with HMC (P < 0.0001). The in vitro system demonstrated age‐related upregulation of pro‐inflammatory cytokines (2‐fold upregulation of interleukin (IL)‐6, IL‐8 mRNA, increased secretion of tumor necrosis factor‐α (TNF‐α) and IL‐6, all P < 0.05) associated with impaired kinetics of myotube differentiation. The HSE biopsy samples showed satellite cell activation (Pax7, P < 0.05) compared with HMC. However, no significant upregulation of the early myogenesis (MyoD and Myf5) markers was evident; only the late myogenesis marker myogenin was upregulated (P < 0.05). Higher activation of the oxidative stress pathway was found in HENS compared with the HSE group. In contrast, there was 10‐fold higher upregulation of HSPA1A a stress‐induced chaperone acting upon misfolded proteins in HSE compared with the HENS group. Conclusions Both pathological and adaptive processes are active in skeletal muscle during healthy ageing. Muscle regeneration pathways are activated during healthy ageing, but there is evidence of dysregulation in sarcopenia. In addition, increased cellular stress, with an impaired oxidative‐stress and mis‐folded protein response (HSPA1A), may be associated with the development of sarcopenia. The in vitro system of young and old myoblasts replicated some of the differences between young and old muscle.https://doi.org/10.1002/jcsm.12252AgeingSatellite cellsSarcopeniaMuscle regenerationCellular stress |
| spellingShingle | Joanna Brzeszczyńska Angelika Meyer Robin McGregor Alain Schilb Simone Degen Valentina Tadini Neil Johns Ramon Langen Annemie Schols David J. Glass Ronenn Roubenoff James A. Ross Kenneth C.H. Fearon Carolyn A. Greig Carsten Jacobi Alterations in the in vitro and in vivo regulation of muscle regeneration in healthy ageing and the influence of sarcopenia Journal of Cachexia, Sarcopenia and Muscle Ageing Satellite cells Sarcopenia Muscle regeneration Cellular stress |
| title | Alterations in the in vitro and in vivo regulation of muscle regeneration in healthy ageing and the influence of sarcopenia |
| title_full | Alterations in the in vitro and in vivo regulation of muscle regeneration in healthy ageing and the influence of sarcopenia |
| title_fullStr | Alterations in the in vitro and in vivo regulation of muscle regeneration in healthy ageing and the influence of sarcopenia |
| title_full_unstemmed | Alterations in the in vitro and in vivo regulation of muscle regeneration in healthy ageing and the influence of sarcopenia |
| title_short | Alterations in the in vitro and in vivo regulation of muscle regeneration in healthy ageing and the influence of sarcopenia |
| title_sort | alterations in the in vitro and in vivo regulation of muscle regeneration in healthy ageing and the influence of sarcopenia |
| topic | Ageing Satellite cells Sarcopenia Muscle regeneration Cellular stress |
| url | https://doi.org/10.1002/jcsm.12252 |
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