2021
DOI: 10.1016/j.cmet.2021.08.017
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Increased fidelity of protein synthesis extends lifespan

Abstract: Summary 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 ar… Show more

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Cited by 88 publications
(73 citation statements)
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References 85 publications
(125 reference statements)
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“…By reducing translation rate in ageing, cells can redistribute energetic resources to the other processes like DNA maintenance, increasing longevity [ 29 ]. Another benefit of the reduced translation rates is the increased translation fidelity, which is considered extremely important in improving longevity [ 65 , 134 ]. Reducing translation rates directly rather than targeting translational control elements may be an appropriate therapeutic intervention for increasing lifespan.…”
Section: Future Research Directions and Areas Of Interestmentioning
confidence: 99%
“…By reducing translation rate in ageing, cells can redistribute energetic resources to the other processes like DNA maintenance, increasing longevity [ 29 ]. Another benefit of the reduced translation rates is the increased translation fidelity, which is considered extremely important in improving longevity [ 65 , 134 ]. Reducing translation rates directly rather than targeting translational control elements may be an appropriate therapeutic intervention for increasing lifespan.…”
Section: Future Research Directions and Areas Of Interestmentioning
confidence: 99%
“…The other important hallmark of aging is the loss of proteostasis [ 1 , 46 ]. Proteostasis pertains to mechanisms that are involved in the stabilization of correctly folded proteins and the degradation of other proteins, including misfolding by proteasomes or lysosomes [ 47 ].…”
Section: Discussionmentioning
confidence: 99%
“…Filipe Cabreiro, Imperial College London, UK, and University of Cologne, Germany, discovered the ribosomal protein S23 (RPS23) K60R mutation to be a hyperaccuracy mutant. RPS23 K60R mutation leads to improved translation accuracy, heat resistance, and longer lifespan in S. pombe, C. elegans and D. melanogaster without reducing translation, making translational fidelity a potential therapeutic target [4]. Notably, protein stability varies across tissues with age independently of cell proliferation rate, which suggests shared and unique aging vulnerabilities of proteins across tissues, as presented by Abigail Buchwalter, University of California, USA [5].…”
Section: Age-dependent Control Of Cellular Maintenance Processesmentioning
confidence: 99%