DIETARY REGULATION OF NUTRIENT ABSORPTION IN AGING

衰老过程中营养吸收的饮食调节

• 批准号: 2052595
• 负责人: RONALDO PARAOAN FERRARIS
• 金额: $ 9.84万
• 依托单位: UNIV OF MED/DENT OF NJ-NJ MEDICAL SCHOOL
• 依托单位国家: 美国
• 财政年份: 1994
• 资助国家: 美国
• 起止时间: 1994-04-01 至 1999-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2052595
• 关键词: age difference; aging; basolateral membrane; brush border membrane; cell migration; dietary aminoacid; dietary carbohydrates; enzyme linked immunosorbent assay; exocrine glands; gastrointestinal epithelium; gastrointestinal nutrient absorption; gastrointestinal system; glucose transport; immunocytochemistry; intestinal mucosa; intestinal villi; laboratory mouse; membrane lipids; membrane permeability; membrane transport proteins; messenger RNA; northern blottings; nutrition of aging; nutrition related tag; small intestines; western blottings

The long-term objective of this application is to understand how intestinal nutrient absorption and its regulation change during the process of aging. Aging is associated with intestinal malabsorption, and the first specific aim is to assess the effects of age on intestinal nutrient absorption and to determine the mechanisms underlying these effects. The absorption rates of various monosaccharides, amino acids and vitamins will be compared between pair-fed aged and young adult mice. To determine whether age-related changes in absorption involve a specific change in number of transporters, the site density of brushborder Na+/D- glucose (SGLT1) and basolateral facilitated D-glucose (GLUT2) transporters will be estimated using specific phlorizin and cytochalasin B binding, respectively, and Western blot analysis. To assess the influence of age on transcription of genes coding for these transporters, levels of SGLT1 and GLUT2 mRNA will be estimated by Northern blot analysis. To evaluate the effects of age-related changes in enterocyte proliferation, immunocytochemistry, autoradiography and ligand-binding techniques will be used to examine the distribution of SGLT1 and GLUT2 along the crypt/villus axis. To determine whether a change in intestinal mass alters nutrient absorption, various indices of mucosal proliferation will be measured. To ascertain whether aging involves a nonspecific change in membrane structure, mucosal permeability or Na + gradient, the lipid composition of, microvilli structure of, passive Permeability of and Na + uptake by the intestinal mucosa will be determined. Aging is associated with impaired adaptive responses, and the second specific aim is to evaluate the effect of age on the dietary regulation of intestinal nutrient transport. Young and aged mice will be fed diets designed to elicit adaptation in nutrient absorption. Changes in nutrient transport rates and certain indices of transporter number, levels of transporter mRNA, mucosal mass and tissue permeability will each be monitored in order to (1) assess the amplitude and pace of adaptation of nutrient transport in aged mice to shifts in diet, and (2) understand the mechanisms for compensation of impaired regulatory processes. This study is significant for the following reasons. First, it will elucidate the mechanisms underlying intestinal malabsorption in the aged, and demonstrate whether dietary manipulations can prevent its onset and/or reduce its severity. Second, it will increase our understanding of how regulatory mechanisms in the small intestine respond to dietary manipulations. Because dietary restriction retards the aging process in rodents, dietary manipulation is increasingly becoming a powerful tool for studying the nature of the aging process. Third, it will demonstrate that aging alters the rate and site of intestinal glucose absorption, factors which determine post-prandial plasma glucose concentrations, thereby contributing to age-related changes in glucose tolerance. Finally, it will yield an important data base for use during development of nutritional interventions in human aging.

该应用程序的长期目标是了解如何 肠道营养吸收及其调节变化 衰老的过程。衰老与肠道吸收不良有关， 第一个具体目标是评估年龄对肠道的影响 营养吸收并确定其背后的机制 影响。各种单糖、氨基酸等的吸收率 将比较配对喂养的老年小鼠和年轻成年小鼠的维生素含量。到 确定与年龄相关的吸收变化是否涉及特定的 转运蛋白数量的变化，刷状缘Na+/D-的位点密度 葡萄糖 (SGLT1) 和基底外侧促进 D-葡萄糖 (GLUT2) 转运蛋白 将使用特定的根皮苷和细胞松弛素 B 结合来估计， 分别和蛋白质印迹分析。评估年龄对的影响 编码这些转运蛋白的基因的转录、SGLT1 的水平和 GLUT2 mRNA 将通过 Northern 印迹分析进行估计。评估 年龄相关的肠上皮细胞增殖变化的影响， 免疫细胞化学、放射自显影和配体结合技术将 用于检查 SGLT1 和 GLUT2 沿隐窝/绒毛的分布 轴。确定肠道质量的变化是否会改变营养 吸收后，将测量粘膜增殖的各种指标。到 确定衰老是否涉及细胞膜的非特异性变化 结构、粘膜通透性或Na+梯度、脂质成分 的、微绒毛结构、被动渗透性和 Na + 吸收 将确定肠粘膜。衰老与以下因素有关 适应性反应受损，第二个具体目标是评估 年龄对肠道营养膳食调节的影响 运输。年轻和年老的小鼠将被喂食旨在引发 营养吸收的适应。养分运输速率的变化和 转运蛋白数量、转运蛋白 mRNA 水平、粘膜的某些指标 将分别监测质量和组织渗透性，以便 (1) 评估 老年小鼠营养运输适应的幅度和速度 饮食的改变，以及（2）了解补偿机制 监管流程受损。本研究对于以下方面具有重要意义 原因。首先，阐明肠道的机制 老年人吸收不良，并证明饮食控制是否有效 可以预防其发作和/或减轻其严重程度。二是会增加 我们对小肠调节机制的理解 对饮食控制做出反应。因为饮食限制会延缓 在啮齿类动物的衰老过程中，饮食控制正日益成为一种 研究衰老过程本质的有力工具。第三，它将 证明衰老会改变肠道葡萄糖的速率和部位 吸收，决定餐后血糖的因素 浓度，从而导致与年龄相关的葡萄糖变化 宽容。最后，它将产生一个重要的数据库供在 人类衰老的营养干预措施的发展。