Article ; Online: Age-dependent loss of Crls1 causes myopathy and skeletal muscle regeneration failure.
Experimental & molecular medicine
2024 Volume 56, Issue 4, Page(s) 922–934
Abstract: Skeletal muscle aging results in the gradual suppression of myogenesis, leading to muscle mass loss. However, the specific role of cardiolipin in myogenesis has not been determined. This study investigated the crucial role of mitochondrial cardiolipin ... ...
| Abstract | Skeletal muscle aging results in the gradual suppression of myogenesis, leading to muscle mass loss. However, the specific role of cardiolipin in myogenesis has not been determined. This study investigated the crucial role of mitochondrial cardiolipin and cardiolipin synthase 1 (Crls1) in age-related muscle deterioration and myogenesis. Our findings demonstrated that cardiolipin and Crls1 are downregulated in aged skeletal muscle. Moreover, the knockdown of Crls1 in myoblasts reduced mitochondrial mass, activity, and OXPHOS complex IV expression and disrupted the structure of the mitochondrial cristae. AAV9-shCrls1-mediated downregulation of Crls1 impaired muscle regeneration in a mouse model of cardiotoxin (CTX)-induced muscle damage, whereas AAV9-mCrls1-mediated Crls1 overexpression improved regeneration. Overall, our results highlight that the age-dependent decrease in CRLS1 expression contributes to muscle loss by diminishing mitochondrial quality in skeletal muscle myoblasts. Hence, modulating CRLS1 expression is a promising therapeutic strategy for mitigating muscle deterioration associated with aging, suggesting potential avenues for developing interventions to improve overall muscle health and quality of life in elderly individuals. |
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| MeSH term(s) | Animals ; Muscle, Skeletal/metabolism ; Muscle, Skeletal/pathology ; Mice ; Regeneration ; Muscular Diseases/metabolism ; Muscular Diseases/etiology ; Muscular Diseases/pathology ; Muscular Diseases/genetics ; Aging/metabolism ; Muscle Development ; Mitochondria/metabolism ; Disease Models, Animal ; Humans ; Cardiolipins/metabolism ; Mitochondrial Proteins/metabolism ; Mitochondrial Proteins/genetics ; Male ; Myoblasts/metabolism |
| Chemical Substances | Cardiolipins ; Mitochondrial Proteins |
| Language | English |
| Publishing date | 2024-04-01 |
| Publishing country | United States |
| Document type | Journal Article ; Research Support, Non-U.S. Gov't |
| ZDB-ID | 1328915-9 |
| ISSN | 2092-6413 ; 1226-3613 ; 0378-8512 |
| ISSN (online) | 2092-6413 |
| ISSN | 1226-3613 ; 0378-8512 |
| DOI | 10.1038/s12276-024-01199-x |
| Database | MEDical Literature Analysis and Retrieval System OnLINE |
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