Differences in the effects of age on intestinal proliferation, crypt fission and apoptosis on the small intestine and the colon of the rat.

The increase in gastrointestinal epithelial tissue mass and the development of the gut can occur through three main mechanisms, namely elevated cell production from the intestinal crypts, by raised crypt number, which occurs through the process of crypt fission or by altered apoptosis. The small bowel and the colon have various rates of these, which were studied in rats of various ages. Wistar rats were fed ad libitum, and were killed at 3, 4, 6, 9, 12, 18, 26 and 48 weeks of age. Tissue was later stained and microdissected and the number of native mitoses and apoptotic figures per crypt and the percentage of crypts in fission were determined. There was an almost linear increase in body weight from 3 to 9 weeks, followed by a more gradual rise until 18 weeks. The weight of the stomach and the small intestine reached maximum values at 9 weeks, whereas the caecum and the colon approached this at 12 weeks. Mitotic activity per crypt in the small intestine increased from 3.8 +/- 0.1 at 3 weeks to 7.8 +/- 0.4 mitoses per crypt (P < 0.001) at 9 weeks and then decreased slightly; crypt fission increased from 4.6% +/- 0.8 at 3 weeks to 8.4 +/- 0.9% at 6 weeks and then decreased gradually reaching a value of 1.5 +/- 0.4% at 48 weeks. Apoptosis also peaked at 6 weeks and was then very low. In the colon, the proliferation decreased from 4.2 +/- 0.2 mitoses per crypt in the young (3 weeks) rat and reached a plateau by 9 weeks (2.5 +/- 0.1 mitoses per crypt, P < 0.001). Crypt fission also declined rapidly in the first 9 weeks (from 67.6 +/- 4.2 to 23.1 +/- 4.6%, P < 0.01) and then continued to decline, although at a lower rate. The crypt fission index at 48 weeks was 9.8 +/- 1.0. Apoptosis in the colon persisted throughout the duration of the study, 0.19 +/- 0.06 apoptotic bodies per crypt were seen at week 48. The development of the small intestine is more dependent on cell proliferation, whereas in the colon crypt fission is far more predominant, with the colon having fission indices approximately six times greater than those of the small intestine. Proliferative activity in the colon was approximately half that of the small intestine.