Age-dependent increase of neurotensin expression in the ileum

The proliferative activity of gut mucosa is increased with aging. Neurotensin (NT), a tridecapeptide localized to the distal small bowel, stimulates growth of gut mucosa; the effects of aging on gut NT are not known. Young (4-mo-old), adult (1-yr-old), and aged (2-yr-old) male Fischer 344 rats were killed; the ileal mucosa was scraped, weighed, and extracted for measurement of NT mRNA by slot-blot and Northern hybridization; and the relative NT transcription rate was determined by a nuclear run-on assay. In addition, NT tissue content and plasma levels were determined by radioimmunoassay, and full-thickness sections of ileum were examined for age- dependent alterations of NT endocrine cell (N-cell) number using immunohistochemical staining. Slot-blot and Northern-blot analyses showed that the steady-state levels of NT mRNA were increased threefold in the adult group and eightfold in the aged rats. In addition, NT peptide content and plasma levels were significantly increased in the aged group. The dramatic increases in the abundance of NT mRNA were not associated with increases in either NT transcription or N-cell number. In summary, we have demonstrated an age-dependent increase in the constitutive levels of ileal NT mRNA that appears not to be due to concomitant increases in transcription, suggesting that NT mRNA is increased by mechanisms involving mainly a posttranscriptional process. In addition, we have shown corresponding increases in the levels of both tissue and plasma NT with aging, indicating that expression of NT does not remain the same throughout life but actually increases with aging in the rat.