Altered controls of proliferation in proximal small intestine of the senescent rat.

The proximal small intestine responds to starvation by rapidly reducing crypt cell proliferation rate and villus cellularity and to resumption of food intake (refeeding) by abruptly increasing proliferation and the number of villus epithelial cells. We show that villus cellularity responds to starvation and refeeding similarly in young and aging animals. However, as compared to young animals, senescent rats showed increased basal DNA synthetic activity, starvation resulted in a smaller decrease in DNA labeling of crypt cells, and refeeding produced an abrupt broadening of the proliferative zone in older animals without concomitant increased numbers of villus cells. Such altered crypt proliferative responses resemble precancerous changes seen in the colon and the aberrant proliferation found in both small and large intestine after administration of the carcinogen dimethylhydrazine.