EFFECT OF AGING ON NEUROTENSIN-STIMULATED GROWTH OF RAT SMALL-INTESTINE

The proliferative activity of gut mucosa is altered with aging; the potential for the aged gut to respond to trophic stimuli is not known. The purpose of this study was to determine whether there are age-related differences in the effects of the trophic gut peptide neurotensin (NT) on the structure and function of small bowel mucosa. NT (300 mu g/kg) or saline (control) was injected subcutaneously at 8-h intervals for 5 days in rats of two age groups, young (2 mo) and aged (24 mo). On day 6, rats were killed, and the gut mucosa (proximal and distal small bowel) was scraped, weighed, and analyzed for DNA, RNA, and protein content and for disaccharidase (sucrase and maltase) activity. In a second experiment, the groups of rats and the protocol for NT administration were identical; however, when the rats were killed, the distal gut was removed for histological evaluation of crypt and villus length (mm) and density (no./cm gut segment) and bromodeoxyuridine immunohistochemistry. NT produced significant increases in mucosal growth (wt, DNA, RNA, and protein) in both age groups when compared with age-matched controls; the increase of growth measurements was the greatest in the small bowel mucosa of the aged rats. In addition, NT increased crypt density in both groups; only the aged group treated with NT demonstrated increases in crypt depth and villus height. Specific activities of sucrase and maltase did not change with NT treatment in either of the age groups. We conclude that the proliferative potential of small bowel mucosa is maintained with aging in response to administration of NT. This effect of NT is predominantly on gut mucosal structure and does not appear to affect function as measured by alterations in disaccharidase activity.