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Increased fidelity of protein synthesis extends lifespan

Martinez-Miguel, Victoria Eugenia, Lujan, Celia, Espie-Caullet, Tristan, Martinez-Martinez, Daniel, Moore, Saul, Backes, Cassandra, Gonzalez, Suam, Galimov, Evgeniy R., Brown, Andre E.X., Halic, Mario, and others. (2021) Increased fidelity of protein synthesis extends lifespan. Cell Metabolism, 33 . pp. 1-13. ISSN 1932-7420. E-ISSN 1932-7420. (doi:10.1016/j.cmet.2021.08.017) (KAR id:90966)


Loss of proteostasis is a fundamental process driving aging. Proteostasis is affected by the accuracy oftranslation, yet the physiological consequence of having fewer protein synthesis errors during multi-cellular organismal aging is poorly understood. Our phylogenetic analysis of RPS23, a key protein in the ribosomaldecoding center, uncovered a lysine residue almost universally conserved across all domains of life, whichis replaced by an arginine in a small number of hyperthermophilic archaea. When introduced into eukaryoticRPS23 homologs, this mutation leads to accurate translation, as well as heat shock resistance and longer life,in yeast, worms, and flies. Furthermore, we show that anti-aging drugs such as rapamycin, Torin1, and tra-metinib reduce translation errors, and that rapamycin extends further organismal longevity in RPS23 hyper-accuracy mutants. This implies a unified mode of action for diverse pharmacological anti-aging therapies.These findings pave the way for identifying novel translation accuracy interventions to improve aging.

Item Type: Article
DOI/Identification number: 10.1016/j.cmet.2021.08.017
Uncontrolled keywords: aging, protein synthesis
Subjects: Q Science > QP Physiology (Living systems) > QP506 Molecular biology
Divisions: Divisions > Division of Natural Sciences > Biosciences
Depositing User: Tobias von der Haar
Date Deposited: 19 Oct 2021 10:54 UTC
Last Modified: 14 Nov 2022 23:13 UTC
Resource URI: (The current URI for this page, for reference purposes)

University of Kent Author Information

von der Haar, Tobias.

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