In rodents and in humans, aging is associated with increased gastrointestinal epithelial cell proliferation and an expanded crypt proliferative compartment similar to that seen in the preneoplastic bowel. We have compared the distribution of a series of cytoskeletal antigens that are modified when colonic cancer cells differentiate in vitro in the colon of young (4-7 month) and aging (22-26 month) Fischer 344 rats. Two such proteins, p52 and p35, (that are increased in cultured senescent cells) differ in their position in the crypt axis and subcellular localization between young and aging rats. In young rats, immunoreactive p52 protein is present solely near the colonic crypt surface epithelium but in aging rats p52 expressing cells are found deeper in crypts. The intracellular localization of p35 also differs markedly in young and aging animals. The distribution of these proteins appears to be a reproducible biomarker of aging. Antigenic changes similar to those observed in aging colons also are seen in crypt cells of patients with ulcerative colitis and in the flat colonic mucosa of patients with adenomatous polyps and colon cancer. The combination of proliferative and differentiation changes suggest that the flat mucosa of the colon of aging rats has preneoplastic features.