Increased fidelity of protein synthesis extends lifespan
Article
Martinez-Miguel, V. E., Lujan, C., Espie-Caullet, T., Martinez-Martinez, D., Moore, S., Backes, C., Gonzalez, S., Galimov, E. R., Brown, A. E. X., Halic, M., Tomita, K., Rallis, C., von der Haar, T., Cabreiro, F. and Bjedov, I. 2021. Increased fidelity of protein synthesis extends lifespan. Cell Metabolism. 33 (11), pp. 2288-2300.e12. https://doi.org/10.1016/j.cmet.2021.08.017
Authors | Martinez-Miguel, V. E., Lujan, C., Espie-Caullet, T., Martinez-Martinez, D., Moore, S., Backes, C., Gonzalez, S., Galimov, E. R., Brown, A. E. X., Halic, M., Tomita, K., Rallis, C., von der Haar, T., Cabreiro, F. and Bjedov, I. |
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Abstract | Loss of proteostasis is a fundamental process driving aging. Proteostasis is affected by the accuracy of translation, 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 ribosomal decoding center, uncovered a lysine residue almost universally conserved across all domains of life, which is replaced by an arginine in a small number of hyperthermophilic archaea. When introduced into eukaryotic RPS23 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 trametinib reduce translation errors, and that rapamycin extends further organismal longevity in RPS23 hyperaccuracy 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. |
Journal | Cell Metabolism |
Journal citation | 33 (11), pp. 2288-2300.e12 |
ISSN | 1550-4131 |
Year | 2021 |
Publisher | Elsevier (Cell Press) |
Publisher's version | License File Access Level Anyone |
Supplemental file | License File Access Level Anyone |
Supplemental file | File Access Level Anyone |
Supplemental file | File Access Level Anyone |
Digital Object Identifier (DOI) | https://doi.org/10.1016/j.cmet.2021.08.017 |
Publication dates | |
Online | 14 Sep 2021 |
02 Nov 2021 | |
Publication process dates | |
Accepted | 30 Aug 2021 |
Deposited | 20 Sep 2021 |
Funder | European Research Council |
Cancer Research UK | |
The Royal Society | |
Wellcome Trust | |
Medical Research Council | |
Biotechnology and Biological Sciences Research Council | |
National Institutes of Health | |
Copyright holder | © 2021 The Author(s) |
https://repository.uel.ac.uk/item/89qx7
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