Reprogramming of ovarian aging epigenome by resveratrol.
Reprogramming of ovarian aging epigenome by resveratrol.
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DOI：
10.1093/pnasnexus/pgac310
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发表时间：
2023-02
期刊：
影响因子：
--
通讯作者：
Liu, Lin
中科院分区：
文献类型：
--
作者：
Gou, Mo;Li, Jie;Yi, Lizhi;Li, Huiyu;Ye, Xiaoying;Wang, Huasong;Liu, Linlin;Sun, Baofa;Zhang, Song;Zhu, Zhengmao;Liu, Jiang;Liu, Lin
白藜芦醇是一种抗衰老、抗氧化和抗炎的天然多酚化合物。越来越多的证据表明，白藜芦醇对改善卵巢功能具有潜在的治疗作用。然而，延长生殖寿命的机制仍然难以捉摸。我们发现白藜芦醇改善卵巢老化转录组，其中一些与甲基组的特定变化有关。除了已知的卵母细胞和颗粒细胞的老化转录组，如氧化还原酶活性、代谢和线粒体功能下降，DNA损伤和凋亡升高外，肌动蛋白细胞骨架随着年龄的增长而明显下调，这些缺陷大多由白藜芦醇修复。此外，白藜芦醇还能降低与衰老相关的肌动蛋白细胞骨架的超甲基化。相反，Tet2的缺失，参与DNA去甲基化，废除白藜芦醇重编程卵巢衰老转录组。与此一致的是，随着小鼠年龄的增长，Tet2缺乏会导致mTOR和Wnt信号的增加，以及DNA修复和肌动蛋白细胞骨架的减少，从而导致其他途径的改变。此外，在白藜芦醇处理的中年小鼠的Tet2缺陷卵母细胞中，与氧化还原酶活性和氧化还原过程相关的基因被高甲基化，这表明Tet2的缺失消除了白藜芦醇的抗氧化作用。综上所述，我们的发现提供了与卵巢衰老相关的转录组和表观遗传变化的全面图景，这些变化可以通过白藜芦醇给药重新编程，并表明Tet2缺乏导致的DNA甲基化异常增加会促进额外的衰老表观基因组，而白藜芦醇无法有效地将其恢复到年轻状态。
Resveratrol is an antiaging, antioxidant, and anti-inflammatory natural polyphenolic compound. Growing evidence indicates that resveratrol has potential therapeutic effects for improving aging ovarian function. However, the mechanisms underlying prolonged reproductive longevity remain elusive. We found that resveratrol ameliorates ovarian aging transcriptome, some of which are associated with specific changes in methylome. In addition to known aging transcriptome of oocytes and granulosa cells such as decline in oxidoreductase activity, metabolism and mitochondria function, and elevated DNA damage and apoptosis, actin cytoskeleton are notably downregulated with age, and these defects are mostly rescued by resveratrol. Moreover, the aging-associated hypermethylation of actin cytoskeleton is decreased by resveratrol. In contrast, deletion of Tet2, involved in DNA demethylation, abrogates resveratrol-reprogrammed ovarian aging transcriptome. Consistently, Tet2 deficiency results in additional altered pathways as shown by increased mTOR and Wnt signaling, as well as reduced DNA repair and actin cytoskeleton with mouse age. Moreover, genes associated with oxidoreductase activity and oxidation–reduction process were hypermethylated in Tet2-deficient oocytes from middle-age mice treated with resveratrol, indicating that loss of Tet2 abolishes the antioxidant effect of resveratrol. Taking together, our finding provides a comprehensive landscape of transcriptome and epigenetic changes associated with ovarian aging that can be reprogrammed by resveratrol administration, and suggests that aberrantly increased DNA methylation by Tet2 deficiency promotes additional aging epigenome that cannot be effectively restored to younger state by resveratrol.
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影响因子：
16.6
作者：
Ferrara-Romeo, Iole;Martinez, Paula;Blasco, Maria A.
通讯作者：
Blasco, Maria A.
影响因子：
--
作者：
Ahmed, Toka A;Ahmed, Sara M;El-Badri, Nagwa
通讯作者：
El-Badri, Nagwa
影响因子：
6.1
作者：
He, Xin;Pei, Shengjie;Li, Duo
通讯作者：
Li, Duo
影响因子：
3.1
作者：
Altun, Tugba;Jindal, Sangita;Pal, Lubna
通讯作者：
Pal, Lubna
DOI：
10.1530/rep-16-0129
发表时间：
2016-09
期刊：
Reproduction (Cambridge, England)
影响因子：
--
作者：
Briley SM;Jasti S;McCracken JM;Hornick JE;Fegley B;Pritchard MT;Duncan FE
通讯作者：
Duncan FE