DNA methylation, an epigenetic mechanism connecting folate to healthy embryonic development and aging.
DNA methylation, an epigenetic mechanism connecting folate to healthy embryonic development and aging.
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DOI：
10.1016/j.jnutbio.2009.06.008
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发表时间：
2009-12
期刊：
影响因子：
--
通讯作者：
Choi SW
中科院分区：
文献类型：
--
作者：
Kim KC;Friso S;Choi SW
实验研究表明，母体在胚胎发育早期暴露于某些环境和饮食因素会影响后代的表型以及以后生活中疾病发展的风险。DNA甲基化是一种表观遗传学现象，在蜜蜂和小鼠模型中都被认为是母体营养物质影响其后代表型的机制。通过DNA甲基化引起的表型变化可以与叶酸代谢联系起来，因为叶酸是一碳代谢的辅酶，直接参与DNA甲基化的甲基转移。在胎儿时期，器官特异性DNA甲基化模式通过表观遗传重编程建立。然而，已建立的DNA甲基化模式不是不可改变的，并且可以在我们的一生中通过环境进行修改。饮食中DNA甲基化的异常变化可能导致包括癌症在内的年龄相关疾病的发展。我们还知道，衰老过程本身伴随着DNA甲基化的改变。DNA甲基转移酶（Dnmts）活性降低可能是衰老过程中基因组DNA甲基化降低的潜在机制，沿着叶酸摄入减少和叶酸代谢改变。在整个衰老过程中观察到某些基因启动子区域的进行性超甲基化，并且由这种表观遗传机制诱导的肿瘤抑制因子的抑制似乎与癌症的发展相关。在这篇综述中，我们通过表观遗传机制，DNA甲基化来解决叶酸对早期发育和衰老的影响。
Experimental studies demonstrated that maternal exposure to certain environmental and dietary factors during early embryonic development can influence the phenotype of offspring as well as the risk of disease development at the later life. DNA methylation, an epigenetic phenomenon, has been suggested as a mechanism by which maternal nutrients affect the phenotype of their offspring in both honeybee and agouti mouse models. Phenotypic changes through DNA methylation can be linked to folate metabolism by the knowledge that folate, a coenzyme of one-carbon metabolism, is directly involved in methyl group transfer for DNA methylation. During the fetal period, organ-specific DNA methylation patterns are established through epigenetic reprogramming. However, established DNA methylation patterns are not immutable and can be modified during our life time by the environment. Aberrant changes in DNA methylation with diet may lead to the development of age-associated diseases including cancer. It is also known that the aging process by itself is accompanied by alterations in DNA methylation. Diminished activity of DNA methyltransferases (Dnmts) can be a potential mechanism for the decreased genomic DNA methylation during aging, along with reduced folate intake and altered folate metabolism. Progressive hypermethylation in promoter regions of certain genes is observed throughout aging and repression of tumor suppressors induced by this epigenetic mechanism appears to be associated with cancer development. In this review we address the effect of folate on early development and aging through an epigenetic mechanism, DNA methylation.
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