Laven Joop S E
Division of Reproductive Endocrinology and Infertility, Department of Obstetrics and Gynaecology, Erasmus Medical Center, Rotterdam, The Netherlands.
Reprod Biomed Online. 2022 Sep;45(3):421-424. doi: 10.1016/j.rbmo.2022.02.027. Epub 2022 Apr 2.
Recent genome-wide association studies have shown that the majority of genes involved in menopause are also instrumental in double-strand break repair and mismatch and base excision repair of DNA. Cumulative DNA damage causes cellular senescence resulting in exhaustion of somatic cell renewal capacity and cellular dysfunction, and eventually to accelerated cell death, generally called ageing. A similar erosion of the genome occurs within the germ cell line and thus in the ovaries. Subsequently, the systemic 'survival' response intentionally suppresses the sex-steroid hormone output, which in turn may contribute to the onset of menopause. The latter occurs in particular when age-dependent DNA damage accumulates. Both effects are expected to synergize to promote ovarian silencing resulting in menopause. Consequently, ageing of the soma seems to be a primary driver for the loss of ovarian function in women. Therefore menopause is the result rather than the cause of ageing.
最近的全基因组关联研究表明，大多数与更年期相关的基因在DNA双链断裂修复、错配修复和碱基切除修复中也发挥着作用。累积的DNA损伤会导致细胞衰老，从而导致体细胞更新能力耗尽和细胞功能障碍，并最终加速细胞死亡，这通常被称为衰老。类似的基因组侵蚀也发生在生殖细胞系中，进而发生在卵巢中。随后，全身的“生存”反应会有意抑制性甾体激素的分泌，这反过来可能会促使更年期的到来。后者尤其在年龄依赖性DNA损伤积累时发生。预计这两种效应会协同作用，促进卵巢沉默，从而导致更年期。因此，体细胞衰老似乎是女性卵巢功能丧失的主要驱动因素。所以，更年期是衰老的结果而非原因。
