Improvement of intestinal stem cells and barrier function via calorie restriction in middle-aged C57BL/6 mice

Abstract This study aimed to reveal the impact of calorie restriction on the intestine via structural and molecular changes in terms of intestinal stem cell (ISC) function, ISC niche, intestinal epithelial barrier function, and intestinal immune function. Female C57BL/6 J mice, aged 12 months, fed a commercial chow were used in this study. The ISC function, ISC niche, intestinal epithelial barrier function, and intestinal immune function were assessed. Calorie restriction reversed aging-induced intestinal shortening and made the crypts shallower. The intestinal epithelial cells (IECs) isolated from the intestine showed a significant increase in the expression levels of stem cell–associated genes in small IECs as detected by flow cytometry. Despite the increase in the number of stem cells and the expression levels of markers, no increase or decrease was found in the enteroid complexity of the small intestine and colonic enteroid formation in vitro. The colonic mucous layer was measured in mice of the CR-treated group to investigate the epithelial barrier function in the colon. The results revealed that the barrier was more complete. The fluorescence intensity of tight junction markers claudin-2 and zonula occludens-1 increased and the mRNA expression profiles of monocyte chemotactic protein 1 and interleukin-6 decreased in the colon of mice in the CR-treated group. The beneficial effects of CR on the colon in terms of the integrity of the mucosal barrier and alleviation of inflammation were confirmed, thus highlighting the importance of modulating the intestinal function in developing effective anti-aging dietary interventions.