Impaired age-associated mitochondrial translation is mitigated by exercise and PGC-1α

de Smalen, Laura M. and Börsch, Anastasiya and Leuchtmann, Aurel B. and Gill, Jonathan F. and Ritz, Danilo and Zavolan, Mihaela and Handschin, Christoph. (2023) Impaired age-associated mitochondrial translation is mitigated by exercise and PGC-1α. Proceedings of the National Academy of Sciences (PNAS), 120 (36). e2302360120.

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Official URL: https://edoc.unibas.ch/95577/

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Sarcopenia, the age-related loss of skeletal muscle mass and function, can dramatically impinge on quality of life and mortality. While mitochondrial dysfunction and imbalanced proteostasis are recognized as hallmarks of sarcopenia, the regulatory and functional link between these processes is underappreciated and unresolved. We therefore investigated how mitochondrial proteostasis, a crucial process that coordinates the expression of nuclear- and mitochondrial-encoded mitochondrial proteins with supercomplex formation and respiratory activity, is affected in skeletal muscle aging. Intriguingly, a robust mitochondrial translation impairment was observed in sarcopenic muscle, which is regulated by the peroxisome proliferator-activated receptor γ coactivator 1 α (PGC-1α) with the estrogen-related receptor α (ERRα). Exercise, a potent inducer of PGC-1α activity, rectifies age-related reduction in mitochondrial translation, in conjunction with quality control pathways. These results highlight the importance of mitochondrial proteostasis in muscle aging, and elucidate regulatory interactions that underlie the powerful benefits of physical activity in this context.
Faculties and Departments:03 Faculty of Medicine > Departement Biomedizin > Associated Research Groups > Pharmakologie (Handschin)
05 Faculty of Science > Departement Biozentrum > Growth & Development > Growth & Development (Handschin)
05 Faculty of Science > Departement Biozentrum > Computational & Systems Biology > Bioinformatics (Zavolan)
UniBasel Contributors:Handschin, Christoph and Zavolan, Mihaela and Börsch, Anastasiya
Item Type:Article, refereed
Article Subtype:Research Article
Publisher:National Academy of Sciences
Note:Publication type according to Uni Basel Research Database: Journal article
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Last Modified:16 Sep 2023 03:10
Deposited On:30 Aug 2023 09:27

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