Various non-enzymic post-translational changes to proteins occur in vivo and some of these progress with aging. These changes are reviewed and linked to a number of age-related diseases, and to alterations in the charge distribution on protein surfaces. Modification by cyanate and by glucose 6-phosphate causes a partial unfolding of proteins, with loss of tertiary structure but retention of secondary structure. These products are reminiscent of the intermediate state observed during folding and unfolding of some proteins.