Colonic proliferation is increased in senescent rats

Our previous studies suggested that crypt size enlarged and that proliferation rate might be greater in the small intestine of rats during senescence. Crypt cell numbers and crypt cell proliferation rates, using the vincristine-induced metaphase arrest technique, now have been measured in the colon of aging and young Fischer 344 rats. The proximal colon of 26-28-mo-old unfasted rats had 10% more crypt cells and a higher proliferative rate than 3-4-mo-old young controls. In the distal colon, the crypt cell proliferation rate in aging rats was 56% greater than in the young. A 3-day fast reduced crypt cell proliferation about fourfold in young rats but only by 20% in aging rats. One-day refeeding abruptly increased the crypt cell population and proliferation rate in rats of both age groups. The crypt zone of proliferating cells from aging rats was broader than that seen in young rats. In addition, starvation lowered colonic crypt cell cycling rate much less in aging than in young animals. We conclude that the colons of aging rats demonstrate a hyperproliferative state and a failure to adapt appropriately to changes in food intake. These observations may be relevant to states of altered proliferation that occur in the premalignant colon.