Reducing mitochondrial ribosomal gene expression does not alter metabolic health or lifespan in mice.

Autor: Reid K; Department of Biology and Ottawa Institute of Systems Biology, University of Ottawa, 30 Marie Curie Private, Ottawa, ON, Canada.; Department of Biochemistry, Microbiology and Immunology, Faculty of Medicine, Ottawa Institute of Systems Biology and the Éric Poulin Centre for Neuromuscular Disease, University of Ottawa, Ottawa, ON, Canada., Daniels EG; Laboratory Genetic Metabolic Diseases, Amsterdam UMC Location University of Amsterdam, Meibergdreef 9, 1105 AZ, Amsterdam, The Netherlands.; Amsterdam Gastroenterology Endocrinology and Metabolism Institute, Amsterdam, The Netherlands., Vasam G; Interdisciplinary School of Health Sciences, University of Ottawa, 451 Smyth Road, Ottawa, ON, K1H 8M5, Canada., Kamble R; Laboratory Genetic Metabolic Diseases, Amsterdam UMC Location University of Amsterdam, Meibergdreef 9, 1105 AZ, Amsterdam, The Netherlands., Janssens GE; Laboratory Genetic Metabolic Diseases, Amsterdam UMC Location University of Amsterdam, Meibergdreef 9, 1105 AZ, Amsterdam, The Netherlands.; Amsterdam Gastroenterology Endocrinology and Metabolism Institute, Amsterdam, The Netherlands., Hu IM; Laboratory Genetic Metabolic Diseases, Amsterdam UMC Location University of Amsterdam, Meibergdreef 9, 1105 AZ, Amsterdam, The Netherlands.; Amsterdam Gastroenterology Endocrinology and Metabolism Institute, Amsterdam, The Netherlands., Green AE; Interdisciplinary School of Health Sciences, University of Ottawa, 451 Smyth Road, Ottawa, ON, K1H 8M5, Canada.; Department of Biochemistry, Microbiology and Immunology, Faculty of Medicine, Ottawa Institute of Systems Biology and the Éric Poulin Centre for Neuromuscular Disease, University of Ottawa, Ottawa, ON, Canada., Houtkooper RH; Laboratory Genetic Metabolic Diseases, Amsterdam UMC Location University of Amsterdam, Meibergdreef 9, 1105 AZ, Amsterdam, The Netherlands. r.h.houtkooper@amsterdamumc.nl.; Amsterdam Gastroenterology Endocrinology and Metabolism Institute, Amsterdam, The Netherlands. r.h.houtkooper@amsterdamumc.nl.; Amsterdam Cardiovascular Sciences Institute, Amsterdam, The Netherlands. r.h.houtkooper@amsterdamumc.nl., Menzies KJ; Interdisciplinary School of Health Sciences, University of Ottawa, 451 Smyth Road, Ottawa, ON, K1H 8M5, Canada. kmenzies@uottawa.ca.; Department of Biochemistry, Microbiology and Immunology, Faculty of Medicine, Ottawa Institute of Systems Biology and the Éric Poulin Centre for Neuromuscular Disease, University of Ottawa, Ottawa, ON, Canada. kmenzies@uottawa.ca.
Jazyk: angličtina
Zdroj: Scientific reports [Sci Rep] 2023 May 24; Vol. 13 (1), pp. 8391. Date of Electronic Publication: 2023 May 24.
DOI: 10.1038/s41598-023-35196-3
Abstrakt: Maintaining mitochondrial function is critical to an improved healthspan and lifespan. Introducing mild stress by inhibiting mitochondrial translation invokes the mitochondrial unfolded protein response (UPR mt ) 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 UPR mt , 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.
(© 2023. The Author(s).)
Databáze: MEDLINE
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