Translation fidelity coevolves with longevity
KE Z; MALLIK P; JOHNSON AB; LUNA F; NEVO E; ZHANG Z; GLADYSHEV VN; SELUANOV A; GORBUNOVA V
WILEY-BLACKWELL PUBLISHING, INC
Lugar: Londres; Año: 2017
Whether errors in protein synthesis play a role in aging has been asubject of intense debate. It has been suggested that rare mistakes in proteinsynthesis in young organisms may result in errors in the protein synthesismachinery, eventually leading to an increasing cascade of errors as organismage. Studies that followed generally failed to identify a dramatic increase in translationerrors with aging. However, whether translation fidelity plays a role in agingremained an open question. To address this issue, we examined the relationshipbetween translation fidelity and maximum lifespan across 17 rodent species withdiverse lifespans. To measure translation fidelity, we utilized sensitive luciferase-basedreporter constructs with mutations in an amino acid residue critical toluciferase activity, wherein misincorporation of amino acids at this mutatedcodon re-activated the luciferase. The frequency of amino acid misincorporationat the first and second codon positions showed strong negative correlation withmaximum lifespan. This correlation remained significant after phylogeneticcorrection, indicating that translation fidelity coevolves with longevity.These results give a new life to the role of protein synthesis errors in aging:Although the error rate may not significantly change with age, the basal rateof translation errors is important in defining lifespan across mammals.