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, Tomita, Kazunori, Rallis, Charalampos ORCID: 0000-0002-4390-0266, von der Haar, Tobias ORCID: 0000-0002-6031-9254, Cabreiro, Filipe and Bjedov, Ivana ORCID: 0000-0001-5894-6016 (2021). Increased fidelity of protein synthesis extends lifespan. Cell Metab., 33 (11). S. 2288 - 2314. CAMBRIDGE: CELL PRESS. ISSN 1932-7420

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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 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: Journal Article
Creators:
CreatorsEmailORCIDORCID Put Code
Martinez-Miguel, Victoria EugeniaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Lujan, CeliaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Espie-Caullet, TristanUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Martinez-Martinez, DanielUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Moore, SaulUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Backes, CassandraUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Gonzalez, SuamUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Galimov, Evgeniy R.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Brown, Andre E. X.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Halic, MarioUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Tomita, KazunoriUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Rallis, CharalamposUNSPECIFIEDorcid.org/0000-0002-4390-0266UNSPECIFIED
von der Haar, TobiasUNSPECIFIEDorcid.org/0000-0002-6031-9254UNSPECIFIED
Cabreiro, FilipeUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Bjedov, IvanaUNSPECIFIEDorcid.org/0000-0001-5894-6016UNSPECIFIED
URN: urn:nbn:de:hbz:38-599259
DOI: 10.1016/j.cmet.2021.08.017
Journal or Publication Title: Cell Metab.
Volume: 33
Number: 11
Page Range: S. 2288 - 2314
Date: 2021
Publisher: CELL PRESS
Place of Publication: CAMBRIDGE
ISSN: 1932-7420
Language: English
Faculty: Unspecified
Divisions: Unspecified
Subjects: no entry
Uncontrolled Keywords:
KeywordsLanguage
TRANSFER-RNA; DIETARY RESTRICTION; GENE-EXPRESSION; ERROR-PRONE; TRANSLATION; EXTENSION; RIBOSOME; MECHANISMS; SELECTION; INSIGHTSMultiple languages
Cell Biology; Endocrinology & MetabolismMultiple languages
URI: http://kups.ub.uni-koeln.de/id/eprint/59925

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