Age-related changes in small intestinal mucosa epithelium architecture and epithelial tight junction in rat models

Abstract

Functions of the intestinal mucosal barrier are often impaired in the elderly and are closely associated with many age-related diseases. However, mechanisms by which aging influences intestinal barrier function still remain unclear. The aim of this study was to investigate age-related changes in small intestinal morphology, bacteria contents and expression of epithelial tight junction (TJ) proteins. Thirty Sprague-Dawley rats were divided into groups: young (3months), adult (12months), and old (24months). The small intestinal mucosal architecture and TJ of intestinal epithelial cells were examined by light microscopy and transmission electron microscopy. Jejunum and cecum contents were cultured to identify and measure bacterial species. mRNA expression of Zonula occludens-1 (ZO-1) and occludin were measured by semi-quantitative RT-PCR. Protein expression of ZO-1 and occludin were detected by immunohistochemistry and Western blot. Normal ileum villi, which were thick and regularly arranged, though increasingly scattered and atrophic in character with shorter and narrower dimensions (P<0.01), were observed in old rats, along with an elevated number of Gram-positive and Gram-negative bacteria in the jejunum. The TJs of intestinal epithelial cells, as detected by transmission electron microscopy, were wider and discontinuous in old rats. Age-induced down-regulation of mRNA expression and decreased protein expression of ZO-1 and occludin were observed in the ileum (P<0.01). Our study indicated that age-related intestinal barrier dysfunction may be associated with mucosal atrophy, damages to TJ structure, increased small intestine bacteria counts, and decreased epithelial TJ protein.