On the Translational Error Theory of Aging

Overview

Journal Proc Natl Acad Sci U S A

Specialty Science

Date 1977 Aug 1

PMID 333438

Citations 14

Authors

P Edelmann

J Gallant

Affiliations

Soon will be listed here.

Abstract

Theoretical treatments of error feedback in translation have revealed that two different modes of behavior are possible, depending on the values of certain parameters. In mode I, the error frequency will rise steadily toward randomness, inevitably reaching whatever value is catastrophic for cell survival; the "error catastrophe" theory of aging implicitly assumes this mode of behavior. In mode II, the error frequency will converge to a stable value, which may or may not have toxic consequences. We have performed an experimental test of the behavior of the translation system in Escherichia coli cells: we altered the system's intrinsic fidelity by means of the error-promoting drug streptomycin, and monitored the kinetics of change in error frequency by means of a specific assay of one kind of mistranslation (incorporation of cysteine into flagellin). We find that the system behaves according to mode II. Moreover, E. coli cells in which the error frequency has stabilized at a value as high as 50 times greater than normal continue to proliferate, albeit abnormally slowly, and their viability is not detectably reduced. Earlier results by Gorini and his associates point in the same direction. These observations diminish the plausibility of the error catastrophe theory of aging.

Citing Articles

Translational error in mice increases with ageing in an organ-dependent manner.

Bottger E, Santhosh Kumar H, Steiner A, Sotirakis E, Thiam K, Isnard Petit P Nat Commun. 2025; 16(1):2069.

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Premature aging in mice with error-prone protein synthesis.

Shcherbakov D, Nigri M, Akbergenov R, Brilkova M, Mantovani M, Isnard Petit P Sci Adv. 2022; 8(9):eabl9051.

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Translation fidelity coevolves with longevity.

Ke Z, Mallik P, Johnson A, Luna F, Nevo E, Zhang Z Aging Cell. 2017; 16(5):988-993.

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Dynamic basis of fidelity and speed in translation: Coordinated multistep mechanisms of elongation and termination.

Prabhakar A, Choi J, Wang J, Petrov A, Puglisi J Protein Sci. 2017; 26(7):1352-1362.

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Mutation and catastrophe in the aging genome.

Milholland B, Suh Y, Vijg J Exp Gerontol. 2017; 94:34-40.

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