Science Department, University College Utrecht, Campusplein 1, 3584 ED Utrecht, The Netherlands.
Biology (Basel). 2014 Jun 18;3(2):403-25. doi: 10.3390/biology3020403.
Recent genome-wide analysis of C-phosphate-G (CpG) sites has shown that the DNA methylome changes with increasing age, giving rise to genome-wide hypomethylation with site‑specific incidences of hypermethylation. This notion has received a lot of attention, as it potentially explains why aged organisms generally have a higher risk of age-related diseases. However, very little is known about the mechanisms that could cause the occurrence of these changes. Moreover, there does not appear to be a clear link between popular theories of aging and alterations in the methylome. Some of the most fruitful of these theories attribute an important role to reactive oxygen species, which seem to be responsible for an increase in oxidative damage to macromolecules, such as DNA, during the lifetime of an organism. In this review, the connection between changes in DNA methylation and these reactive oxygen species is discussed, as well as the effect of these changes on health. Deeper insights into the nature, causes and consequences of the aging methylome might provide a deeper understanding of the molecular mechanisms of aging and eventually contribute to the development of new diagnostic and therapeutic tools.
最近对 C-磷酸-G（CpG）位点的全基因组分析表明，DNA 甲基化组随年龄的增长而变化，导致全基因组低甲基化和特定部位的高甲基化。这一观点引起了广泛关注，因为它可能解释了为什么衰老的生物体通常患与年龄相关的疾病的风险更高。然而，对于可能导致这些变化发生的机制，我们知之甚少。此外，衰老的流行理论与甲基化组的改变之间似乎没有明显的联系。其中一些最有成效的理论将重要作用归因于活性氧，这些活性氧似乎在生物体的一生中负责增加对大分子（如 DNA）的氧化损伤。在这篇综述中，讨论了 DNA 甲基化的变化与这些活性氧之间的联系，以及这些变化对健康的影响。更深入地了解衰老甲基化组的性质、原因和后果，可能会深入了解衰老的分子机制，并最终有助于开发新的诊断和治疗工具。
