Genetic and epigenetic interactions between foliate and aging in carcinogenesis
Genetic and epigenetic interactions between foliate and aging in carcinogenesis
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DOI：
10.1093/jn/135.12.2967s
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发表时间：
2005-12-01
影响因子：
4.2
通讯作者：
Choi, SW
中科院分区：
文献类型：
--
作者：
Jang, HR;Mason, JB;Choi, SW
叶酸是对结肠癌保护作用最强的饮食成分之一，叶酸状态降低与患结肠癌的风险增加有关。年龄也被认为是结肠癌发生的最重要的危险因素之一。因此，确定衰老过程是否影响结肠中的叶酸代谢，以及补充叶酸是否可以防止与衰老相关的癌前效应，是相当有意义的。我们实验室最近的研究表明，老年大鼠的结肠粘膜比青年大鼠更容易受到叶酸耗竭的影响。叶酸的耗尽会导致结肠中叶酸形式的改变，以及尿嘧啶掺入DNA的增加，这是结肠癌发生的一个据称的机制。然而，适量的叶酸补充消除了老年大鼠结肠中叶酸状态不足的证据，这表明年龄与结肠中叶酸状态之间的关系可能是衰老调节结直肠癌风险的机制之一。叶酸和衰老之间的相互作用还影响一系列表观遗传和遗传现象，如尿嘧啶错掺、DNA甲基化、蛋白质甲基化、线粒体缺失和关键基因表达，这些可能与癌症的发生有关。衰老和饮食不足的叶酸可能相互作用，共同导致叶酸代谢紊乱，从而引发随后的分子异常，这可能会促进癌症的发生。然而，补充叶酸似乎可以逆转衰老的这些不利影响，这可能具有重要意义，因为后者是一个不可改变的风险因素。
Folate is among the most strongly implicated dietary components to convey protection against colon cancer, and diminished folate status is associated with an enhanced risk of colon cancer. Age is also regarded as one of the most important risk factors for colonic carcinogenesis. It is therefore of considerable interest to determine whether the process of aging influences folate metabolism in the colon and whether folate supplementation might prevent the procarcinogenic effects associated with aging. Recent studies in our laboratory demonstrated that the colonic mucosa of elder rats is more susceptible to folate depletion than that of young rats. Depletion of folate results in a shift in the forms of folate in the colon as well as increased uracil incorporation into DNA, a purported mechanism for colonic carcinogenesis. However, modest folate supplementation eliminates evidence of inadequate folate status in the colons of elder rats, suggesting that the relation between age and folate status in the colon might be one mechanism by which aging modulates colorectal cancer risk. Interactions between folate and aging also affect a spectrum of epigenetic and genetic phenomena such as uracil misincorporation, DNA methylation, protein methylation, mitochondrial deletion, and critical gene expression, which could be related to carcinogenesis. Aging and inadequate dietary folate may interact and collectively induce derangements in folate metabolism, thereby provoking subsequent molecular aberrations, which may enhance carcinogenesis. However, folate supplementation appears to reverse these adverse effects of aging, which is potentially of substantial import because the latter is an unmodifiable risk factor.