Irisin ameliorates age‐associated sarcopenia and metabolic dysfunction
Abstract Background Age‐associated sarcopenia is characterized of progressed loss of skeletal muscle power, mass, and function, which affects human physical activity and life quality. Besides, accompanied with sarcopenia, aged population also faces a series of metabolic dysfunctions. Irisin, the cle...
| Main Authors: | , , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Wiley
2023-02-01
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| Series: | Journal of Cachexia, Sarcopenia and Muscle |
| Subjects: | |
| Online Access: | https://doi.org/10.1002/jcsm.13141 |
| _version_ | 1797805595979415552 |
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| author | Mingwei Guo Jing Yao Jin Li Jun Zhang Dongmei Wang Hui Zuo Yi Zhang Bo Xu Yinzhao Zhong Fei Shen Jian Lu Shuzhe Ding Cheng Hu Lingyan Xu Junjie Xiao Xinran Ma |
| author_facet | Mingwei Guo Jing Yao Jin Li Jun Zhang Dongmei Wang Hui Zuo Yi Zhang Bo Xu Yinzhao Zhong Fei Shen Jian Lu Shuzhe Ding Cheng Hu Lingyan Xu Junjie Xiao Xinran Ma |
| author_sort | Mingwei Guo |
| collection | DOAJ |
| description | Abstract Background Age‐associated sarcopenia is characterized of progressed loss of skeletal muscle power, mass, and function, which affects human physical activity and life quality. Besides, accompanied with sarcopenia, aged population also faces a series of metabolic dysfunctions. Irisin, the cleaved form of fibronectin type III domain‐containing protein 5 (FNDC5), is a myokine induced by exercise and has been shown to exert multiple beneficial effects on health. The goal of the study is to investigate the alterations of Fndc5/irisin in skeletal muscles during ageing and whether irisin administration could ameliorate age‐associated sarcopenia and metabolic dysfunction. Methods The mRNA and protein levels of FNDC5/irisin in skeletal muscle and serum from 2‐ and 24‐month‐old mice or human subjects were analysed using qRT‐PCR and western blot. FNDC5/irisin knockout mice were generated to investigate the consequences of FNDC5/irisin deletion on skeletal muscle mass, as well as morphological and molecular changes in muscle during ageing via histological and molecular analysis. To identify the therapeutic effects of chronic irisin treatment in mice during ageing, in vivo intraperitoneal administration of 2 mg/kg recombinant irisin was performed three times per week in ageing mice (14‐month‐old) for 4 months or in aged mice (22‐month‐old) for 1 month to systematically investigate irisin's effects on age‐associated sarcopenia and metabolic performances, including grip strength, body weights, body composition, insulin sensitivity, energy expenditure, serum parameters and phenotypical and molecular changes in fat and liver. Results We showed that the expression levels of irisin, as well as its precursor Fndc5, were reduced at mRNA and protein expression levels in muscle during ageing. In addition, via phenotypic analysis of FNDC5/irisin knockout mice, we found that FNDC5/irisin deficiency in aged mice exhibited aggravated muscle atrophy including smaller grip strength (−3.23%, P < 0.05), muscle weights (quadriceps femoris [QU]: −20.05%; gastrocnemius [GAS]: −17.91%; tibialis anterior [TA]: −19.51%, all P < 0.05), fibre size (QU: P < 0.01) and worse molecular phenotypes compared with wild‐type mice. We then delivered recombinant irisin protein intraperitoneally into ageing or aged mice and found that it could improve sarcopenia with grip strength (+18.42%, P < 0.01 or +13.88%, P < 0.01), muscle weights (QU: +9.02%, P < 0.01 or +16.39%, P < 0.05), fibre size (QU: both P < 0.05) and molecular phenotypes and alleviated age‐associated fat tissues expansion, insulin resistance and hepatic steatosis (all P < 0.05), accompanied with altered gene signatures. Conclusions Together, this study revealed the importance of irisin in the maintenance of muscle physiology and systematic energy homeostasis during ageing and suggested a potent therapeutic strategy against age‐associated metabolic diseases via irisin administration. |
| first_indexed | 2024-03-13T05:54:26Z |
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| id | doaj.art-f1801bc1fcbb47b0914afdf6951006ad |
| institution | Directory Open Access Journal |
| issn | 2190-5991 2190-6009 |
| language | English |
| last_indexed | 2024-03-13T05:54:26Z |
| publishDate | 2023-02-01 |
| publisher | Wiley |
| record_format | Article |
| series | Journal of Cachexia, Sarcopenia and Muscle |
| spelling | doaj.art-f1801bc1fcbb47b0914afdf6951006ad2023-06-13T07:50:50ZengWileyJournal of Cachexia, Sarcopenia and Muscle2190-59912190-60092023-02-0114139140510.1002/jcsm.13141Irisin ameliorates age‐associated sarcopenia and metabolic dysfunctionMingwei Guo0Jing Yao1Jin Li2Jun Zhang3Dongmei Wang4Hui Zuo5Yi Zhang6Bo Xu7Yinzhao Zhong8Fei Shen9Jian Lu10Shuzhe Ding11Cheng Hu12Lingyan Xu13Junjie Xiao14Xinran Ma15Shanghai Key Laboratory of Regulatory Biology, Institute of Biomedical Sciences and School of Life Sciences East China Normal University Shanghai ChinaShanghai Key Laboratory of Regulatory Biology, Institute of Biomedical Sciences and School of Life Sciences East China Normal University Shanghai ChinaCardiac Regeneration and Ageing Lab, Institute of Cardiovascular Sciences, Shanghai Engineering Research Center of Organ Repair, School of Life Science Shanghai University Shanghai ChinaShanghai Key Laboratory of Regulatory Biology, Institute of Biomedical Sciences and School of Life Sciences East China Normal University Shanghai ChinaShanghai Key Laboratory of Regulatory Biology, Institute of Biomedical Sciences and School of Life Sciences East China Normal University Shanghai ChinaShanghai Key Laboratory of Regulatory Biology, Institute of Biomedical Sciences and School of Life Sciences East China Normal University Shanghai ChinaShanghai Diabetes Institute, Shanghai Key Laboratory of Diabetes Mellitus, Shanghai Clinical Centre for Diabetes Shanghai Jiao Tong University Affiliated Sixth People's Hospital Shanghai ChinaShanghai Diabetes Institute, Shanghai Key Laboratory of Diabetes Mellitus, Shanghai Clinical Centre for Diabetes Shanghai Jiao Tong University Affiliated Sixth People's Hospital Shanghai ChinaShanghai Key Laboratory of Regulatory Biology, Institute of Biomedical Sciences and School of Life Sciences East China Normal University Shanghai ChinaKey Laboratory of Adolescent Health Assessment and Exercise Intervention of Ministry of Education, College of Physical Education and Health East China Normal University Shanghai ChinaKey Laboratory of Adolescent Health Assessment and Exercise Intervention of Ministry of Education, College of Physical Education and Health East China Normal University Shanghai ChinaKey Laboratory of Adolescent Health Assessment and Exercise Intervention of Ministry of Education, College of Physical Education and Health East China Normal University Shanghai ChinaShanghai Diabetes Institute, Shanghai Key Laboratory of Diabetes Mellitus, Shanghai Clinical Centre for Diabetes Shanghai Jiao Tong University Affiliated Sixth People's Hospital Shanghai ChinaShanghai Key Laboratory of Regulatory Biology, Institute of Biomedical Sciences and School of Life Sciences East China Normal University Shanghai ChinaCardiac Regeneration and Ageing Lab, Institute of Cardiovascular Sciences, Shanghai Engineering Research Center of Organ Repair, School of Life Science Shanghai University Shanghai ChinaShanghai Key Laboratory of Regulatory Biology, Institute of Biomedical Sciences and School of Life Sciences East China Normal University Shanghai ChinaAbstract Background Age‐associated sarcopenia is characterized of progressed loss of skeletal muscle power, mass, and function, which affects human physical activity and life quality. Besides, accompanied with sarcopenia, aged population also faces a series of metabolic dysfunctions. Irisin, the cleaved form of fibronectin type III domain‐containing protein 5 (FNDC5), is a myokine induced by exercise and has been shown to exert multiple beneficial effects on health. The goal of the study is to investigate the alterations of Fndc5/irisin in skeletal muscles during ageing and whether irisin administration could ameliorate age‐associated sarcopenia and metabolic dysfunction. Methods The mRNA and protein levels of FNDC5/irisin in skeletal muscle and serum from 2‐ and 24‐month‐old mice or human subjects were analysed using qRT‐PCR and western blot. FNDC5/irisin knockout mice were generated to investigate the consequences of FNDC5/irisin deletion on skeletal muscle mass, as well as morphological and molecular changes in muscle during ageing via histological and molecular analysis. To identify the therapeutic effects of chronic irisin treatment in mice during ageing, in vivo intraperitoneal administration of 2 mg/kg recombinant irisin was performed three times per week in ageing mice (14‐month‐old) for 4 months or in aged mice (22‐month‐old) for 1 month to systematically investigate irisin's effects on age‐associated sarcopenia and metabolic performances, including grip strength, body weights, body composition, insulin sensitivity, energy expenditure, serum parameters and phenotypical and molecular changes in fat and liver. Results We showed that the expression levels of irisin, as well as its precursor Fndc5, were reduced at mRNA and protein expression levels in muscle during ageing. In addition, via phenotypic analysis of FNDC5/irisin knockout mice, we found that FNDC5/irisin deficiency in aged mice exhibited aggravated muscle atrophy including smaller grip strength (−3.23%, P < 0.05), muscle weights (quadriceps femoris [QU]: −20.05%; gastrocnemius [GAS]: −17.91%; tibialis anterior [TA]: −19.51%, all P < 0.05), fibre size (QU: P < 0.01) and worse molecular phenotypes compared with wild‐type mice. We then delivered recombinant irisin protein intraperitoneally into ageing or aged mice and found that it could improve sarcopenia with grip strength (+18.42%, P < 0.01 or +13.88%, P < 0.01), muscle weights (QU: +9.02%, P < 0.01 or +16.39%, P < 0.05), fibre size (QU: both P < 0.05) and molecular phenotypes and alleviated age‐associated fat tissues expansion, insulin resistance and hepatic steatosis (all P < 0.05), accompanied with altered gene signatures. Conclusions Together, this study revealed the importance of irisin in the maintenance of muscle physiology and systematic energy homeostasis during ageing and suggested a potent therapeutic strategy against age‐associated metabolic diseases via irisin administration.https://doi.org/10.1002/jcsm.13141FNDC5irisinageingsarcopeniametabolic dysfunction |
| spellingShingle | Mingwei Guo Jing Yao Jin Li Jun Zhang Dongmei Wang Hui Zuo Yi Zhang Bo Xu Yinzhao Zhong Fei Shen Jian Lu Shuzhe Ding Cheng Hu Lingyan Xu Junjie Xiao Xinran Ma Irisin ameliorates age‐associated sarcopenia and metabolic dysfunction Journal of Cachexia, Sarcopenia and Muscle FNDC5 irisin ageing sarcopenia metabolic dysfunction |
| title | Irisin ameliorates age‐associated sarcopenia and metabolic dysfunction |
| title_full | Irisin ameliorates age‐associated sarcopenia and metabolic dysfunction |
| title_fullStr | Irisin ameliorates age‐associated sarcopenia and metabolic dysfunction |
| title_full_unstemmed | Irisin ameliorates age‐associated sarcopenia and metabolic dysfunction |
| title_short | Irisin ameliorates age‐associated sarcopenia and metabolic dysfunction |
| title_sort | irisin ameliorates age associated sarcopenia and metabolic dysfunction |
| topic | FNDC5 irisin ageing sarcopenia metabolic dysfunction |
| url | https://doi.org/10.1002/jcsm.13141 |
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