Random errors in protein synthesis activate an age-dependent program of muscle atrophy in mice
Autor: | David P. Wolfer, Dimitri Shcherbakov, Anne Eckert, Martina Nigri, Kader Thiam, James M. Moore, Rashid Akbergenov, Patricia Isnard-Petit, Stephan Frank, Amandine Grimm, Lisa Michelle Restelli, Petra Seebeck, Erik C. Böttger |
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Přispěvatelé: | University of Zurich, Böttger, Erik C |
Rok vydání: | 2021 |
Předmět: |
Male
0301 basic medicine Genetically modified mouse Aging 10017 Institute of Anatomy QH301-705.5 Medicine (miscellaneous) 610 Medicine & health 1100 General Agricultural and Biological Sciences Biology medicine.disease_cause Article General Biochemistry Genetics and Molecular Biology Mice 03 medical and health sciences 0302 clinical medicine 1300 General Biochemistry Genetics and Molecular Biology medicine Animals Biology (General) Transcriptomics PI3K/AKT/mTOR pathway Mutation 10179 Institute of Medical Microbiology Skeletal muscle 2701 Medicine (miscellaneous) Translation (biology) Ribosome Phenotype Muscle atrophy Protein quality control Cell biology Mice Inbred C57BL Muscular Atrophy 030104 developmental biology medicine.anatomical_structure Protein Biosynthesis FOXO3 570 Life sciences biology Female medicine.symptom Transcriptome General Agricultural and Biological Sciences Ribosomes 030217 neurology & neurosurgery |
Zdroj: | Communications Biology, Vol 4, Iss 1, Pp 1-11 (2021) Communications Biology, 4 (1) Communications Biology |
ISSN: | 2399-3642 |
DOI: | 10.1038/s42003-021-02204-z |
Popis: | Random errors in protein synthesis are prevalent and ubiquitous, yet their effect on organismal health has remained enigmatic for over five decades. Here, we studied whether mice carrying the ribosomal ambiguity (ram) mutation Rps2-A226Y, recently shown to increase the inborn error rate of mammalian translation, if at all viable, present any specific, possibly aging-related, phenotype. We introduced Rps2-A226Y using a Cre/loxP strategy. Resulting transgenic mice were mosaic and showed a muscle-related phenotype with reduced grip strength. Analysis of gene expression in skeletal muscle using RNA-Seq revealed transcriptomic changes occurring in an age-dependent manner, involving an interplay of PGC1α, FOXO3, mTOR, and glucocorticoids as key signaling pathways, and finally resulting in activation of a muscle atrophy program. Our results highlight the relevance of translation accuracy, and show how disturbances thereof may contribute to age-related pathologies. Communications Biology, 4 (1) ISSN:2399-3642 |
Databáze: | OpenAIRE |
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