The interconnections between somatic and ovarian aging in murine models.
The interconnections between somatic and ovarian aging in murine models.
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DOI：
10.1093/gerona/glaa258
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发表时间：
2020-10
期刊：
影响因子：
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通讯作者：
A. Schneider;T. Saccon;D. N. Garcia;B. Zanini;J. Isola;Jéssica D Hense;J. A. Alvarado-Rincón;M. Cavalcante;J. Mason;Michael B. Stout;A. Bartke;M. Masternak
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文献类型：
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作者：
A. Schneider;T. Saccon;D. N. Garcia;B. Zanini;J. Isola;Jéssica D Hense;J. A. Alvarado-Rincón;M. Cavalcante;J. Mason;Michael B. Stout;A. Bartke;M. Masternak
雌性哺乳动物天生具有有限的原始卵泡卵巢储备。这些原始卵泡在整个生殖周期中缓慢激活，从而决定了生命周期的长度。一旦原始卵泡耗尽，女性就会进入更年期，这与几种代谢紊乱和更高的死亡风险有关。早在保护区耗尽之前，雌性的生育能力和健康状况就会严重下降。因此，人们已经做出了重大努力来揭示促进卵巢衰老和功能不全的机制。在这篇综述中，我们解释了长寿小鼠模型如何为卵巢衰老的调节提供见解。现在有压倒性的证据表明，大多数延长寿命的策略和长寿的突变模型同时延缓卵巢衰老。因此，似乎调节体细胞衰老的相同机制也可能调节卵巢衰老和生殖细胞衰竭。我们探讨了几种潜在的促进机制，包括胰岛素抵抗、炎症和DNA损伤；所有这些都是包括卵巢在内的全身细胞衰老的标志。这些发现与衰老的一次性体细胞理论一致，该理论指出了生长、繁殖和DNA修复之间的权衡。因此，延缓卵巢衰老不仅可以增加中年女性的生育窗口期，还可以积极预防绝经相关的全身健康参数下降，压缩女性中老年发病期。
The mammalian female is born with a limited ovarian reserve of primordial follicles. These primordial follicles are slowly activated throughout the reproductive lifecycle, thereby determining lifecycle length. Once primordial follicles are exhausted, women undergo menopause, which is associated with several metabolic perturbations and a higher mortality risk. Long before exhaustion of the reserve, females experience severe declines in fertility and health. As such, significant efforts have been made to unravel the mechanisms that promote ovarian aging and insufficiency. In this review, we explain how long-living murine models can provide insights in the regulation of ovarian aging. There is now overwhelming evidence that most lifespan-extending strategies, and long-living mutant models simultaneously delay ovarian aging. Therefore, it appears that the same mechanisms that regulate somatic aging may also be modulating ovarian aging and germ cell exhaustion. We explore several potential contributing mechanisms including insulin resistance, inflammation, and DNA damage; all of which are hallmarks of cellular aging throughout the body including the ovary. These findings are in alignment with the disposable soma theory of aging, which dictates a trade-off between growth, reproduction and DNA repair. Therefore, delaying ovarian aging will not only increase the fertility window of middle age females, but may also actively prevent menopausal-related decline in systemic health parameters, compressing the period of morbidity in mid-to-late life in females.