Reducing mitochondrial ribosomal gene expression does not alter metabolic health or lifespan in mice
Abstract Maintaining mitochondrial function is critical to an improved healthspan and lifespan. Introducing mild stress by inhibiting mitochondrial translation invokes the mitochondrial unfolded protein response (UPRmt) and increases lifespan in several animal models. Notably, lower mitochondrial ri...
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| Format: | Article |
| Language: | English |
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Nature Portfolio
2023-05-01
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| Series: | Scientific Reports |
| Online Access: | https://doi.org/10.1038/s41598-023-35196-3 |
| _version_ | 1797817959821869056 |
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| author | Kim Reid Eileen G. Daniels Goutham Vasam Rashmi Kamble Georges E. Janssens Iman M. Hu Alexander E. Green Riekelt H. Houtkooper Keir J. Menzies |
| author_facet | Kim Reid Eileen G. Daniels Goutham Vasam Rashmi Kamble Georges E. Janssens Iman M. Hu Alexander E. Green Riekelt H. Houtkooper Keir J. Menzies |
| author_sort | Kim Reid |
| collection | DOAJ |
| description | Abstract Maintaining mitochondrial function is critical to an improved healthspan and lifespan. Introducing mild stress by inhibiting mitochondrial translation invokes the mitochondrial unfolded protein response (UPRmt) and increases lifespan in several animal models. Notably, lower mitochondrial ribosomal protein (MRP) expression also correlates with increased lifespan in a reference population of mice. In this study, we tested whether partially reducing the gene expression of a critical MRP, Mrpl54, reduced mitochondrial DNA-encoded protein content, induced the UPRmt, and affected lifespan or metabolic health using germline heterozygous Mrpl54 mice. Despite reduced Mrpl54 expression in multiple organs and a reduction in mitochondrial-encoded protein expression in myoblasts, we identified few significant differences between male or female Mrpl54 +/− and wild type mice in initial body composition, respiratory parameters, energy intake and expenditure, or ambulatory motion. We also observed no differences in glucose or insulin tolerance, treadmill endurance, cold tolerance, heart rate, or blood pressure. There were no differences in median life expectancy or maximum lifespan. Overall, we demonstrate that genetic manipulation of Mrpl54 expression reduces mitochondrial-encoded protein content but is not sufficient to improve healthspan in otherwise healthy and unstressed mice. |
| first_indexed | 2024-03-13T09:01:09Z |
| format | Article |
| id | doaj.art-04f22427ca1c4e4aba80208d5951efcd |
| institution | Directory Open Access Journal |
| issn | 2045-2322 |
| language | English |
| last_indexed | 2024-03-13T09:01:09Z |
| publishDate | 2023-05-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Scientific Reports |
| spelling | doaj.art-04f22427ca1c4e4aba80208d5951efcd2023-05-28T11:17:11ZengNature PortfolioScientific Reports2045-23222023-05-0113111510.1038/s41598-023-35196-3Reducing mitochondrial ribosomal gene expression does not alter metabolic health or lifespan in miceKim Reid0Eileen G. Daniels1Goutham Vasam2Rashmi Kamble3Georges E. Janssens4Iman M. Hu5Alexander E. Green6Riekelt H. Houtkooper7Keir J. Menzies8Department of Biology and Ottawa Institute of Systems Biology, University of OttawaLaboratory Genetic Metabolic Diseases, Amsterdam UMC Location University of AmsterdamInterdisciplinary School of Health Sciences, University of OttawaLaboratory Genetic Metabolic Diseases, Amsterdam UMC Location University of AmsterdamLaboratory Genetic Metabolic Diseases, Amsterdam UMC Location University of AmsterdamLaboratory Genetic Metabolic Diseases, Amsterdam UMC Location University of AmsterdamInterdisciplinary School of Health Sciences, University of OttawaLaboratory Genetic Metabolic Diseases, Amsterdam UMC Location University of AmsterdamInterdisciplinary School of Health Sciences, University of OttawaAbstract Maintaining mitochondrial function is critical to an improved healthspan and lifespan. Introducing mild stress by inhibiting mitochondrial translation invokes the mitochondrial unfolded protein response (UPRmt) and increases lifespan in several animal models. Notably, lower mitochondrial ribosomal protein (MRP) expression also correlates with increased lifespan in a reference population of mice. In this study, we tested whether partially reducing the gene expression of a critical MRP, Mrpl54, reduced mitochondrial DNA-encoded protein content, induced the UPRmt, and affected lifespan or metabolic health using germline heterozygous Mrpl54 mice. Despite reduced Mrpl54 expression in multiple organs and a reduction in mitochondrial-encoded protein expression in myoblasts, we identified few significant differences between male or female Mrpl54 +/− and wild type mice in initial body composition, respiratory parameters, energy intake and expenditure, or ambulatory motion. We also observed no differences in glucose or insulin tolerance, treadmill endurance, cold tolerance, heart rate, or blood pressure. There were no differences in median life expectancy or maximum lifespan. Overall, we demonstrate that genetic manipulation of Mrpl54 expression reduces mitochondrial-encoded protein content but is not sufficient to improve healthspan in otherwise healthy and unstressed mice.https://doi.org/10.1038/s41598-023-35196-3 |
| spellingShingle | Kim Reid Eileen G. Daniels Goutham Vasam Rashmi Kamble Georges E. Janssens Iman M. Hu Alexander E. Green Riekelt H. Houtkooper Keir J. Menzies Reducing mitochondrial ribosomal gene expression does not alter metabolic health or lifespan in mice Scientific Reports |
| title | Reducing mitochondrial ribosomal gene expression does not alter metabolic health or lifespan in mice |
| title_full | Reducing mitochondrial ribosomal gene expression does not alter metabolic health or lifespan in mice |
| title_fullStr | Reducing mitochondrial ribosomal gene expression does not alter metabolic health or lifespan in mice |
| title_full_unstemmed | Reducing mitochondrial ribosomal gene expression does not alter metabolic health or lifespan in mice |
| title_short | Reducing mitochondrial ribosomal gene expression does not alter metabolic health or lifespan in mice |
| title_sort | reducing mitochondrial ribosomal gene expression does not alter metabolic health or lifespan in mice |
| url | https://doi.org/10.1038/s41598-023-35196-3 |
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