Accelerated Sarcopenia Phenotype in the DJ-1/<i>Park7</i>-Knockout Zebrafish
Age-dependent loss of muscle mass and function is associated with oxidative stress. DJ-1/<i>Park7</i> acts as an antioxidant through multiple signalling pathways. DJ-1-knockout zebrafish show a decline in swimming performance and loss of weight gain between 6 and 9 months of age. Here, w...
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| Main Authors: | , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2024-12-01
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| Series: | Antioxidants |
| Subjects: | |
| Online Access: | https://www.mdpi.com/2076-3921/13/12/1509 |
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| Summary: | Age-dependent loss of muscle mass and function is associated with oxidative stress. DJ-1/<i>Park7</i> acts as an antioxidant through multiple signalling pathways. DJ-1-knockout zebrafish show a decline in swimming performance and loss of weight gain between 6 and 9 months of age. Here, we address the degree to which this is associated with muscle degeneration and identify molecular changes preceding dysregulation of muscle performance. Loss of DJ-1 reduced the skeletal muscle fibre cross-section area. The highly mitochondrial-dependent red slow muscle was more affected than the white muscle, and degeneration of sub-sarcolemma red muscle mitochondria was observed. Using TandemMassTag-based quantitative proteomics, we identified a total of 3721 proteins in the multiplex sample of 4 and 12-month-old muscles. A total of 68 proteins, mainly associated with inflammation and mitochondrial function, were dysregulated in the young DJ-1-null adults, with Annexin A3, Sphingomyelin phosphodiesterase acid-like 3B, Complement C3a, and 2,4-dienoyl CoA reductase 1 being the most affected. The loss of DJ-1 also accelerated molecular features associated with sarcopenia, such as a decrease in the NAD<sup>+</sup>/NADH ratio and a reduction in Prostaglandin reductase 2 and Cytosolic glycerol-3-phosphate dehydrogenase levels. In view of the experimental power of zebrafish, the DJ-1-null zebrafish makes a valuable model for understanding the connection between oxidative stress and age-dependent muscle loss and function. |
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| ISSN: | 2076-3921 |