EXPRESSION OF PROTEASE GENES IN THE GASTRIC-MUCOSA DURING AGING

The current investigation examines the changes in the expression of pe psinogen C and cathepsin D and E genes in the gastric mucosa during ag ing and following physiological stimuli of fasting and refeeding. Nort hern blot analysis of gastric mucosal RNA, isolated from overnight fas ted 6-, 12-, and 24-month-old male Fischer 344 rats, revealed that alt hough steady-state mRNA levels of each of these proteases remained ess entially unchanged between 6 and 12 months of age, in 24-month-old rat s the levels were decreased by about 60%, when compared with their you nger counterparts. Interestingly, the relative concentration of beta-a ctin mRNA-but not 18s rRNA-in 12- and 24-month-old rats was also decre ased by 23% and 37%, respectively, when compared with 6-month-old anim als. In the next set of experiments, groups of young (3 month) and age d (24 month) rats were either fed throughout (controls) or fasted for 48 h and then fed for 6 h and 24 h. Gastric mucosal RNA from each grou p was assayed for steady-state mRNA levels of pepsinogen C and catheps in D. Results showed that, whereas in young rats fasting decreased pep sinogen C and cathepsin D mRNAs by 80-85%, in aged rats only pepsinoge n mRNA was significantly decreased (45%), when compared with the corre sponding initial fed controls. In both age groups, refeeding increased pepsinogen C mRNA concentration essentially to the respective initial fed levels. In contrast, cathepsin D mRNA levels in the gastric mucos a of aged rats was affected neither by fasting nor by refeeding. Our c urrent data show that aging not only diminishes the expression of prot ease genes in the gastric mucosa, but also the expression of one of it s structural genes, beta-actin. In addition, responsiveness of these p rotease genes to the physiological stimuli of fasting and refeeding is also attenuated by aging. We postulate that these age-related changes may in part be due to diminished differentiation of gastric mucosal c ells.