Shimoda Nobuyoshi, Izawa Toshiaki, Yoshizawa Akio, Yokoi Hayoto, Kikuchi Yutaka, Hashimoto Naohiro
Department of Regenerative Medicine, National Institute for Longevity Sciences, National Center for Geriatrics and Gerontology, 36-3 Gengo, Morioka, Ōbu, Aichi, 474-8522, Japan,
Age (Dordr). 2014 Feb;36(1):103-15. doi: 10.1007/s11357-013-9548-5. Epub 2013 Jun 5.
Age-related changes in DNA methylation have been demonstrated in mammals, but it remains unclear as to the generality of this phenomenon in vertebrates, which is a criterion for the fundamental cause of senescence. Here we showed that the zebrafish genome gradually and clearly lost methylcytosine in somatic cells, but not in male germ cells during aging, and that age-dependent hypomethylation preferentially occurred at a particular domain called the CpG island shore, which is associated with vertebrates' genes and has been shown to be hypomethylated in humans with age. We also found that two CpG island shores hypomethylated in zebrafish oocytes were de novo methylated in fertilized eggs, which suggests that the zebrafish epigenome is reset upon fertilization, enabling new generations to restart with a heavily methylated genome. Furthermore, we observed an increase in cleavage of the zebrafish genome to an oligonucleosome length in somatic cells from the age of 12 months, which is suggestive of an elevated rate of apoptosis in the senescent stage.
DNA甲基化的年龄相关变化已在哺乳动物中得到证实，但在脊椎动物中这种现象的普遍性仍不清楚，而这是衰老根本原因的一个标准。在这里，我们表明，斑马鱼基因组在衰老过程中，体细胞中的甲基胞嘧啶逐渐且明显丢失，但雄性生殖细胞中没有，并且年龄依赖性低甲基化优先发生在一个名为CpG岛岸的特定区域，该区域与脊椎动物的基因相关，并且已显示在人类中会随着年龄增长而发生低甲基化。我们还发现，斑马鱼卵母细胞中两个低甲基化的CpG岛岸在受精卵中发生了从头甲基化，这表明斑马鱼表观基因组在受精时被重置，使新一代能够以高度甲基化的基因组重新开始。此外，我们观察到，从12个月大开始，斑马鱼体细胞中基因组切割成寡核小体长度的情况增加，这表明衰老阶段细胞凋亡率升高。
