Effect of aging on folate metabolism in the colon

描述(由申请人提供)： 结直肠癌仍然是#年癌症死亡的第二大常见原因。 美国和许多发达国家都是如此。存在以下风险 发生结直肠癌似乎与以下几个因素密切相关 环境因素，其中最显著的是饮食模式，在 在这方面，有来自许多不同类型研究的相当多的数据 这表明患癌症的风险与习惯成反比 叶酸的饮食摄入量。年龄也是结直肠癌的一个非常重要的决定因素 患癌症的风险；超过40岁的人患癌症的风险每过十年就会翻一番。 我们实验室的初步动物研究表明，一种机械联系 年龄增加和叶酸代谢完整性降低之间的关系 由此表明，年龄对结直肠癌风险的影响可能 至少部分地通过叶酸代谢的变化来调节。 本申请概述了在实验室啮齿动物模型中进行的研究 旨在清楚地定义老化过程和 叶酸在感兴趣的目标组织，结肠粘膜中的代谢。我们 建议确定老年是否改变了数量和质量 结肠中叶酸代谢的某些方面，使其 易发生叶酸耗竭，并检查年长动物是否 因此需要较高水平的膳食叶酸来维持充足的 结肠粘膜中的细胞叶酸水平。此外，还有几个 DNA的分子像差与其发病机制有关 致癌作用以前被认为是叶酸的后果。 因此我们将确定年龄和年龄之间的相互关系， 叶酸状态和这些分子异常的演化。

DESCRIPTION (provided by applicant): Colorectal cancer remains the second most common cause of cancer mortality in both the United States and in much of the developed world. The risk of developing colorectal cancer appears to be strongly linked to several environmental factors, the most notable of which is dietary patterns, and in this regard there is considerable data from many different types of studies indicating that the risk of the cancer is inversely related to habitual dietary intake of folate. Age is also a very strong determinant of colorectal cancer risk; past the age of 40 the risk doubles with each passing decade. Preliminary animal studies in our laboratory have indicated a mechanistic link between advancing age and diminished integrity of folate metabolism in the colon; thereby suggesting that the impact of age on colorectal cancer risk may be mediated, at least in part, through changes in folate metabolism. This application outlines studies in a laboratory rodent model which are designed to clearly define the relationship between the aging process and folate metabolism in the target tissue of interest, the colonic mucosa. We propose to determine whether elder age alters quantitative and qualitative aspects of folate metabolism in the colon in such a way as to make it more susceptible to folate depletion and to examine whether the elder animal therefore requires a higher level of dietary folate to maintain adequate levels of cellular folate in the colonic mucosa. In addition, several molecular aberrations of DNA which are implicated as mechanisms of carcinogenesis have been previously identified as consequences of folate depletion and we will therefore determine the inter-relationships between age, folate status and the evolution of these molecular anomalies.