衰老大鼠卵巢功能下降与自噬基因甲基化。
Decreased ovarian function and autophagy gene methylation in aging rats.
机构信息
Department of Physiology, Harbin Medical University, Harbin, 150086, China.
出版信息
J Ovarian Res. 2020 Feb 3;13(1):12. doi: 10.1186/s13048-020-0615-0.
BACKGROUND
Degeneration of ovarian function is an obvious feature of female aging. In addition, studies have shown that autophagy decreases with age, and DNA methylation is a hallmark epigenetic pattern during aging. However, it is not clear whether the expression and DNA methylation of autophagy genes are involved in the declines in ovarian function that occur during aging.
RESULTS
Three groups of rats were used: 6-month-old (6 M) rats, 12-month-old (12 M) rats and 24-month-old (24 M) rats. Serum E levels and the mRNA and protein expression levels of Atg5, Atg12, Atg16L, Beclin1 and Lc3B were significantly decreased in aged rats. In addition, the methylation levels of the Atg5 gene were significantly increased in aged rats. The expression of the Dnmt1 and Dnmt2 genes decreased with aging; however, the expression of the Dnmt3A and Dnmt3B genes gradually increased with aging.
CONCLUSIONS
Decreased autophagic activity was involved in the declines in ovarian function in aging rats. Upregulation of the DNA methyltransferases Dnmt3A and Dnmt3B may have led to methylation of the autophagy genes Atg5 and Lc3B to ultimately cause the observed decreases in autophagic activity.
背景
卵巢功能的退化是女性衰老的一个明显特征。此外，研究表明自噬随年龄的增长而减少，而 DNA 甲基化是衰老过程中一种典型的表观遗传模式。然而，自噬基因的表达和 DNA 甲基化是否参与衰老过程中卵巢功能的下降尚不清楚。
结果
使用了三组大鼠：6 月龄（6M）大鼠、12 月龄（12M）大鼠和 24 月龄（24M）大鼠。血清 E 水平以及 Atg5、Atg12、Atg16L、Beclin1 和 Lc3B 的 mRNA 和蛋白表达水平在老年大鼠中均显著降低。此外，Atg5 基因的甲基化水平在老年大鼠中显著增加。Dnmt1 和 Dnmt2 基因的表达随年龄的增长而减少；然而，Dnmt3A 和 Dnmt3B 基因的表达随年龄的增长而逐渐增加。
结论
自噬活性的降低参与了衰老大鼠卵巢功能的下降。DNA 甲基转移酶 Dnmt3A 和 Dnmt3B 的上调可能导致自噬基因 Atg5 和 Lc3B 的甲基化，最终导致观察到的自噬活性降低。
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