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

The proliferative activity of gut mucosa is altered with aging; the po tential for the aged gut to respond to trophic stimuli is not known. T he purpose of this study was to determine whether there are age-relate d differences in the effects of the trophic gut peptide neurotensin (N T) on the structure and function of small bowel mucosa. NT (300 mu g/k g) or saline (control) was injected subcutaneously at 8-h intervals fo r 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 c ontent and for disaccharidase (sucrase and maltase) activity. In a sec ond experiment, the groups of rats and the protocol for NT administrat ion were identical; however, when the rats were killed, the distal gut was removed for histological evaluation of crypt and villus length (m m) and density (no./cm gut segment) and bromodeoxyuridine immunohistoc hemistry. 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 d ensity in both groups; only the aged group treated with NT demonstrate d increases in crypt depth and villus height. Specific activities of s ucrase and maltase did not change with NT treatment in either of the a ge 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 n ot appear to affect function as measured by alterations in disaccharid ase activity.