Effect of aging on folate metabolism in the colon

描述（由申请人提供）： 结直肠癌仍然是第二个最常见的癌症死亡原因， 在美国和许多发达国家都是如此。的风险 结直肠癌的发生似乎与几个 环境因素，其中最显着的是饮食模式， 在这方面，许多不同类型的研究提供了大量数据 这表明癌症的风险与习惯性癌症呈负相关。 叶酸的饮食摄入量。年龄也是结直肠癌的一个非常强的决定因素 癌症风险; 40岁以后，风险每过十年增加一倍。 我们实验室的初步动物研究表明， 年龄增长和叶酸代谢的完整性降低之间的关系 因此，年龄对结直肠癌风险的影响可能 至少部分通过叶酸代谢的变化来介导。 本申请概述了在实验室啮齿动物模型中的研究， 旨在明确定义衰老过程与 叶酸代谢的目标组织，结肠粘膜。我们 建议确定老年是否改变了数量和质量 叶酸在结肠代谢的方面，以这种方式，使它更 易受叶酸消耗的影响，并检查老年动物是否 因此，需要更高水平的膳食叶酸，以维持足够的 结肠粘膜中的细胞叶酸水平。此外，几个 DNA的分子畸变，这与 致癌作用以前被认为是叶酸的结果 因此我们将确定年龄之间的相互关系 叶酸状态和这些分子异常的演变。

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.