On the translational error theory of aging

Abstract

Theoretical treatments of error feedback in translation have revealed that 2 different modes of behavior are possible, depedning on 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. An experimental test of the behavior of the translation system in Escherichia coli cells was done. The system''s intrinsic fidelity was altered by the error-promoting drug streptomycin, and the kinetics of change in error frequency were monitored by means of a specific assay of 1 kind of mistranslation (incorporation of cysteine into flagellin). The system behaved according to model II. E. coli cells in which the error frequency stabilized at a value as high as 50 times greater than normal continued to proliferate, albeit abnormally slowly, and their viability was not detectably reduced. These observations diminished the plausibility of the error catastrophe theory of aging.