Diet restriction increases apoptosis in the gut of aging rats.

Previous studies have shown that epithelial cell production rates are increased throughout the gastrointestinal tract in aging rats. We tested the hypothesis that alteration in cell death (apoptosis) might be involved. Fischer 344 rats aged 4-5 months and 24-25 months fed ad libitum (AL) or calorie restricted (CR) to 60% of the AL intake were studied. Epithelial cell apoptosis was determined by a terminal deoxyuridine nucleotidyl nick end labeling (TUNEL) technique validated in our laboratory, and the expression of four members of the Bcl-2 family was evaluated by Western blotting in the small intestine and colon. The apoptotic index was low in young and aging AL and young CR rats. However, CR in aging rats was associated with a significantly higher apoptotic index in the jejunum and colon. The expression of the Bcl-2 family of genes was unchanged. Enhanced apoptosis in CR may protect the gastrointestinal tract from accumulation of DNA-altered cells during the aging process.