Age-Associated Remodeling of the Intestinal Epithelial Barrier
Age-Associated Remodeling of the Intestinal Epithelial Barrier
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DOI：
10.1093/gerona/glt106
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发表时间：
2013-09-01
影响因子：
5.1
通讯作者：
Greenwood-Van Meerveld, Beverley
中科院分区：
文献类型：
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作者：
Lee Tran;Greenwood-Van Meerveld, Beverley
胃肠道疾病在老年人中很常见；然而，人们对导致胃肠道脆弱的确切衰老特征(S)知之甚少。最近的证据表明，胃肠道疾病患者的肠道通透性增加。在这里，我们提出的假设是，肠道屏障的破坏与衰老有关。我们的结果表明，从老年狒狒收集的结肠活检组织的通透性明显高于年轻狒狒。此外，老年动物的结肠组织减少了闭锁蛋白-1、闭锁蛋白和连接黏附分子-A紧密连接蛋白的表达，而增加了Claudin-2的表达。与幼龄相比，老年狒狒的结肠活检组织中miR-29a和炎性细胞因子干扰素-6、IL-6和IL-1的表达也上调。这些结果首次表明，老年人对胃肠功能障碍的易感性的一个关键因素可能是通过与年龄相关的肠上皮紧密连接蛋白重塑而增加的结肠通透性。
Disorders of the gastrointestinal tract are common in the elderly people; however, the precise trait(s) of aging that contribute to the vulnerability of the gastrointestinal tract are poorly understood. Recent evidence suggests that patients with gastrointestinal disorders have increased intestinal permeability. Here, we address the hypothesis that disruption of the intestinal barrier is associated with aging. Our results demonstrated that permeability was significantly higher in colonic biopsies collected from old baboons compared with young baboons. Additionally, colonic tissue from the older animals had decreased zonula occluden-1, occludin, and junctional adhesion molecule-A tight junction protein expression and increased claudin-2 expression. Upregulation of miR-29a and inflammatory cytokines IFN-, IL-6, and IL-1 was also found in colonic biopsies from old baboons relative to young baboons. These results show for the first time that a pivotal contributing factor to geriatric vulnerability to gastrointestinal dysfunction may be increased colonic permeability via age-associated remodeling of intestinal epithelial tight junction proteins.