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DIETARY REGULATION OF NUTRIENT ABSORPTION IN AGING

衰老过程中营养吸收的饮食调节

基本信息

批准号：
2667621
负责人：
RONALDO PARAOAN FERRARIS
金额：
$ 10.36万
依托单位：
UNIV OF MED/DENT OF NJ-NJ MEDICAL SCHOOL
依托单位国家：
美国
项目类别：
财政年份：
1994
资助国家：
美国
起止时间：
1994-04-01 至 2000-02-29
项目状态：
已结题

项目摘要

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.

本应用程序的长期目标是了解如何小肠营养吸收及其调节变化老化的过程。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，并确定这些机制方面的影响.各种单糖、氨基酸和将在成对喂养的老年和年轻成年小鼠之间比较维生素。到确定与年龄相关的吸收变化是否涉及特定的转运体数量、刷状缘Na+/D-位点密度的变化葡萄糖（SGLT 1）和基底外侧易化D-葡萄糖（GLUT 2）转运蛋白将使用特异性根皮苷和细胞松弛素B结合来估计， Western blot分析。评估年龄对编码这些转运蛋白的基因的转录，SGLT 1和将通过北方印迹分析估计GLUT 2 mRNA。评价肠上皮细胞增殖中年龄相关变化的影响，免疫细胞化学，放射自显影和配体结合技术将是用于检查SGLT 1和GLUT 2沿着隐窝/绒毛的分布轴线为了确定肠道质量的变化是否会改变营养成分，吸收，将测量粘膜增殖的各种指数。到确定老化是否涉及膜的非特异性变化结构、粘膜渗透性或Na +梯度、脂质组成的微绒毛结构、被动渗透性和Na +吸收将测定肠粘膜。衰老与适应性反应受损，第二个具体目标是评估年龄对肠道营养素饮食调节的影响运输年轻和年老的小鼠将被喂食旨在引起适应营养吸收。营养物质运输速率的变化，转运蛋白数量、转运蛋白mRNA水平、粘膜将分别监测质量和组织渗透性，以便（1）评估老年小鼠营养转运适应性变化幅度和速度饮食的变化，（2）了解补偿的机制，监管程序受损。本研究对以下几个方面具有重要意义原因首先，它将阐明肠道的机制，吸收不良的老年人，并证明是否饮食操纵可以预防其发作和/或降低其严重性。二是会增加我们对小肠调节机制的理解对饮食控制有反应因为饮食限制阻碍了在啮齿类动物的衰老过程中，饮食操纵越来越成为一种研究衰老过程的有力工具。三是将表明衰老改变了肠道葡萄糖的速率和位置，吸收，决定餐后血糖的因素浓度，从而促进葡萄糖的年龄相关变化宽容最后，它将产生一个重要的数据库，发展人类衰老的营养干预措施。