Senescence of growth-arrested Escherichia coli cells is like mandatory aging in higher eukaryotes, accompanied by increased oxidative modifications of macromolecules. Similar to aged flies, this senescence-related oxidation targets enzymes of the Krebs cycle. Additional targets include the universal stress protein A, the Hsp70 chaperone DnaK, translation elongation factors, and histone-like proteins. However, during the early stages of stasis, protein oxidation is more general and affects a large number of proteins. Attempts to correlate this protein oxidation with a reduced activity of the antioxidant defense systems or an increased tendency of the respiratory apparatus to produce reactive oxygen species (ROS) have generated conflicting results. Instead, recent data indicate that oxidation of proteins may occur in the absence of an increased oxidative stress and is rather caused by an increased production of substrates available for oxidative attack. Misfolded and aberrant proteins appear to be such substrates and the production of aberrant polypeptides surge during the early stages of stasis due to a reduced translational fidelity. The data point to a novel mechanism involved in protein oxidation that has not been considered previously in aging research.