Downregulation of mitochondrial metabolism is a driver for fast skeletal muscle loss during mouse aging
Abstract Skeletal muscle aging is characterized by the loss of muscle mass, strength and function, mainly attributed to the atrophy of glycolytic fibers. Underlying mechanisms driving the skeletal muscle functional impairment are yet to be elucidated. To unbiasedly uncover its molecular mechanisms,...
| Main Authors: | , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Nature Portfolio
2023-12-01
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| Series: | Communications Biology |
| Online Access: | https://doi.org/10.1038/s42003-023-05595-3 |
| _version_ | 1797397831502266368 |
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| author | Raquel Fernando Anastasia V. Shindyapina Mario Ost Didac Santesmasses Yan Hu Alexander Tyshkovskiy Sun Hee Yim Jürgen Weiss Vadim N. Gladyshev Tilman Grune José Pedro Castro |
| author_facet | Raquel Fernando Anastasia V. Shindyapina Mario Ost Didac Santesmasses Yan Hu Alexander Tyshkovskiy Sun Hee Yim Jürgen Weiss Vadim N. Gladyshev Tilman Grune José Pedro Castro |
| author_sort | Raquel Fernando |
| collection | DOAJ |
| description | Abstract Skeletal muscle aging is characterized by the loss of muscle mass, strength and function, mainly attributed to the atrophy of glycolytic fibers. Underlying mechanisms driving the skeletal muscle functional impairment are yet to be elucidated. To unbiasedly uncover its molecular mechanisms, we recurred to gene expression and metabolite profiling in a glycolytic muscle, Extensor digitorum longus (EDL), from young and aged C57BL/6JRj mice. Employing multi-omics approaches we found that the main age-related changes are connected to mitochondria, exhibiting a downregulation in mitochondrial processes. Consistent is the altered mitochondrial morphology. We further compared our mouse EDL aging signature with human data from the GTEx database, reinforcing the idea that our model may recapitulate muscle loss in humans. We are able to show that age-related mitochondrial downregulation is likely to be detrimental, as gene expression signatures from commonly used lifespan extending interventions displayed the opposite direction compared to our EDL aging signature. |
| first_indexed | 2024-03-09T01:15:53Z |
| format | Article |
| id | doaj.art-b1e477911453427b854cf104b5383a76 |
| institution | Directory Open Access Journal |
| issn | 2399-3642 |
| language | English |
| last_indexed | 2024-03-09T01:15:53Z |
| publishDate | 2023-12-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Communications Biology |
| spelling | doaj.art-b1e477911453427b854cf104b5383a762023-12-10T12:28:21ZengNature PortfolioCommunications Biology2399-36422023-12-016111110.1038/s42003-023-05595-3Downregulation of mitochondrial metabolism is a driver for fast skeletal muscle loss during mouse agingRaquel Fernando0Anastasia V. Shindyapina1Mario Ost2Didac Santesmasses3Yan Hu4Alexander Tyshkovskiy5Sun Hee Yim6Jürgen Weiss7Vadim N. Gladyshev8Tilman Grune9José Pedro Castro10Department of Molecular Toxicology, German Institute of Human Nutrition Potsdam-RehbrückeDivision of Genetics, Department of Medicine, Brigham and Women’s Hospital, Harvard Medical SchoolDepartment of Physiology of Energy Metabolism, German Institute of Human Nutrition Potsdam-RehbrückeDivision of Genetics, Department of Medicine, Brigham and Women’s Hospital, Harvard Medical SchoolDivision of Genetics, Department of Medicine, Brigham and Women’s Hospital, Harvard Medical SchoolDivision of Genetics, Department of Medicine, Brigham and Women’s Hospital, Harvard Medical SchoolDivision of Genetics, Department of Medicine, Brigham and Women’s Hospital, Harvard Medical SchoolGerman Center for Diabetes Research (DZD)Division of Genetics, Department of Medicine, Brigham and Women’s Hospital, Harvard Medical SchoolDepartment of Molecular Toxicology, German Institute of Human Nutrition Potsdam-RehbrückeDepartment of Molecular Toxicology, German Institute of Human Nutrition Potsdam-RehbrückeAbstract Skeletal muscle aging is characterized by the loss of muscle mass, strength and function, mainly attributed to the atrophy of glycolytic fibers. Underlying mechanisms driving the skeletal muscle functional impairment are yet to be elucidated. To unbiasedly uncover its molecular mechanisms, we recurred to gene expression and metabolite profiling in a glycolytic muscle, Extensor digitorum longus (EDL), from young and aged C57BL/6JRj mice. Employing multi-omics approaches we found that the main age-related changes are connected to mitochondria, exhibiting a downregulation in mitochondrial processes. Consistent is the altered mitochondrial morphology. We further compared our mouse EDL aging signature with human data from the GTEx database, reinforcing the idea that our model may recapitulate muscle loss in humans. We are able to show that age-related mitochondrial downregulation is likely to be detrimental, as gene expression signatures from commonly used lifespan extending interventions displayed the opposite direction compared to our EDL aging signature.https://doi.org/10.1038/s42003-023-05595-3 |
| spellingShingle | Raquel Fernando Anastasia V. Shindyapina Mario Ost Didac Santesmasses Yan Hu Alexander Tyshkovskiy Sun Hee Yim Jürgen Weiss Vadim N. Gladyshev Tilman Grune José Pedro Castro Downregulation of mitochondrial metabolism is a driver for fast skeletal muscle loss during mouse aging Communications Biology |
| title | Downregulation of mitochondrial metabolism is a driver for fast skeletal muscle loss during mouse aging |
| title_full | Downregulation of mitochondrial metabolism is a driver for fast skeletal muscle loss during mouse aging |
| title_fullStr | Downregulation of mitochondrial metabolism is a driver for fast skeletal muscle loss during mouse aging |
| title_full_unstemmed | Downregulation of mitochondrial metabolism is a driver for fast skeletal muscle loss during mouse aging |
| title_short | Downregulation of mitochondrial metabolism is a driver for fast skeletal muscle loss during mouse aging |
| title_sort | downregulation of mitochondrial metabolism is a driver for fast skeletal muscle loss during mouse aging |
| url | https://doi.org/10.1038/s42003-023-05595-3 |
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