Translation fidelity coevolves with longevity

Zhonghe Ke, Pramit Mallik, Adam B. Johnson, Facundo Luna, Eviatar Nevo, Zhengdong Zhang, Vadim N. Gladyshev, Andrei Seluanov, Vera Gorbunova

Research output: Contribution to journalArticle

17 Citations (Scopus)

Abstract

Whether errors in protein synthesis play a role in aging has been a subject of intense debate. It has been suggested that rare mistakes in protein synthesis in young organisms may result in errors in the protein synthesis machinery, eventually leading to an increasing cascade of errors as organisms age. Studies that followed generally failed to identify a dramatic increase in translation errors with aging. However, whether translation fidelity plays a role in aging remained an open question. To address this issue, we examined the relationship between translation fidelity and maximum lifespan across 17 rodent species with diverse lifespans. To measure translation fidelity, we utilized sensitive luciferase-based reporter constructs with mutations in an amino acid residue critical to luciferase activity, wherein misincorporation of amino acids at this mutated codon re-activated the luciferase. The frequency of amino acid misincorporation at the first and second codon positions showed strong negative correlation with maximum lifespan. This correlation remained significant after phylogenetic correction, indicating that translation fidelity coevolves with longevity. These results give new life to the role of protein synthesis errors in aging: Although the error rate may not significantly change with age, the basal rate of translation errors is important in defining lifespan across mammals.

Original languageEnglish (US)
JournalAging Cell
DOIs
StateAccepted/In press - 2017

Fingerprint

Luciferases
Amino Acids
Codon
Proteins
Mammals
Rodentia
Mutation

Keywords

  • Aging
  • Comparative biology
  • Longevity
  • Translation fidelity

ASJC Scopus subject areas

  • Aging
  • Cell Biology

Cite this

Ke, Z., Mallik, P., Johnson, A. B., Luna, F., Nevo, E., Zhang, Z., ... Gorbunova, V. (Accepted/In press). Translation fidelity coevolves with longevity. Aging Cell. https://doi.org/10.1111/acel.12628

Translation fidelity coevolves with longevity. / Ke, Zhonghe; Mallik, Pramit; Johnson, Adam B.; Luna, Facundo; Nevo, Eviatar; Zhang, Zhengdong; Gladyshev, Vadim N.; Seluanov, Andrei; Gorbunova, Vera.

In: Aging Cell, 2017.

Research output: Contribution to journalArticle

Ke, Z, Mallik, P, Johnson, AB, Luna, F, Nevo, E, Zhang, Z, Gladyshev, VN, Seluanov, A & Gorbunova, V 2017, 'Translation fidelity coevolves with longevity', Aging Cell. https://doi.org/10.1111/acel.12628
Ke, Zhonghe ; Mallik, Pramit ; Johnson, Adam B. ; Luna, Facundo ; Nevo, Eviatar ; Zhang, Zhengdong ; Gladyshev, Vadim N. ; Seluanov, Andrei ; Gorbunova, Vera. / Translation fidelity coevolves with longevity. In: Aging Cell. 2017.
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