Author:
Reid Kim,Daniels Eileen G.,Vasam Goutham,Kamble Rashmi,Janssens Georges E.,Hu Iman M.,Green Alexander E.,Houtkooper Riekelt H.,Menzies Keir J.
Abstract
AbstractMaintaining 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.
Funder
Natural Sciences and Engineering Research Council of Canada
University of Amsterdam Lustrum 385
University of Ottawa Brain and Mind Research Institute uOttawa Eric Poulin Centre for Neuromuscular Disease Scholarship in Translational Research Award
NWO Talent Programme Vidi
Canadian Institutes of Health Research
Publisher
Springer Science and Business Media LLC
Cited by
1 articles.
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