National Engineering Laboratory for Animal Breeding, Key Laboratory of Animal Genetics and Breeding of the Ministry of Agriculture, Beijing Key Laboratory for Animal Genetic Improvement, College of Animal Science and Technology, China Agricultural University, Beijing, China.
Key Laboratory of Agricultural Animal Genetics, Breeding and Reproduction, Education Ministry of China, College of Animal Science and Technology, Huazhong Agricultural University, Wuhan, China.
Aging Cell. 2021 Feb;20(2):e13291. doi: 10.1111/acel.13291. Epub 2021 Jan 15.
The fecundity reduction with aging is referred as the reproductive aging which comes earlier than that of chronological aging. Since humans have postponed their childbearing age, to prolong the reproductive age becomes urgent agenda for reproductive biologists. In the current study, we examined the potential associations of α-ketoglutarate (α-KG) and reproductive aging in mammals including mice, swine, and humans. There is a clear tendency of reduced α-KG level with aging in the follicle fluids of human. To explore the mechanisms, mice were selected as the convenient animal model. It is observed that a long term of α-KG administration preserves the ovarian function, the quality and quantity of oocytes as well as the telomere maintaining system in mice. α-KG suppresses ATP synthase and alterations of the energy metabolism trigger the nutritional sensors to down-regulate mTOR pathway. These events not only benefit the general aging process but also maintain ovarian function and delay the reproductive decline. Considering the safety of the α-KG as a naturally occurring molecule in energy metabolism, its utility in reproduction of large mammals including humans deserves further investigation.
生育力随年龄下降被称为生殖衰老，它比生理年龄衰老出现得更早。由于人类已经推迟了生育年龄，延长生殖年龄成为生殖生物学家的紧迫议程。在目前的研究中，我们检查了哺乳动物（包括小鼠、猪和人类）中α-酮戊二酸（α-KG）和生殖衰老的潜在关联。人类卵泡液中α-KG 水平随年龄下降的趋势非常明显。为了探索其机制，选择了小鼠作为方便的动物模型。结果观察到，长期给予α-KG 可保持卵巢功能、卵母细胞的质量和数量以及端粒维持系统。α-KG 抑制 ATP 合酶，能量代谢的改变触发营养传感器下调 mTOR 通路。这些事件不仅有益于一般的衰老过程，而且还维持卵巢功能，延缓生殖衰退。考虑到α-KG 作为能量代谢中天然存在的分子的安全性，其在包括人类在内的大型哺乳动物生殖中的应用值得进一步研究。
