On the translational error theory of aging

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.