Kobayashi Hiroshi, Umetani Mai, Nishio Miki, Shigetomi Hiroshi, Imanaka Shogo, Hashimoto Hiratsugu
Department of Gynecology and Reproductive Medicine, Ms.Clinic MayOne, 871-1 Shijo-cho, Kashihara 634-0813, Japan.
Department of Obstetrics and Gynecology, Nara Medical University, 840 Shijo-cho, Kashihara 634-8522, Japan.
Cells. 2025 Jun 6;14(12):858. doi: 10.3390/cells14120858.
The endometrium is essential for reproductive function, supporting implantation and pregnancy through mechanisms such as hormonal responsiveness, immune regulation, and tissue regeneration. Aging disrupts these processes, with cellular senescence-marked by irreversible cell cycle arrest due to DNA damage and oxidative stress-being a key contributor. While senescence aids in tumor suppression and tissue repair, its dysregulation impairs endometrial function. Central to this regulation are p53, AMPK, and mTOR, which coordinate stress responses, metabolic regulation, and proliferation control. p53 activates AMPK and inhibits mTOR, promoting energy conservation and limiting senescence. AMPK also suppresses mTOR, reducing age-related dysfunction. This p53-AMPK-mTOR axis, along with autophagy, governs cell fate in response to stress and nutrient status. Although moderate senescence supports endometrial function, excessive accumulation can hinder fertility. Understanding these molecular interactions may advance fertility treatments and strategies to counteract reproductive aging.
子宫内膜对于生殖功能至关重要，它通过激素反应性、免疫调节和组织再生等机制支持着床和妊娠。衰老会破坏这些过程，细胞衰老（以DNA损伤和氧化应激导致的不可逆细胞周期停滞为特征）是一个关键因素。虽然衰老有助于肿瘤抑制和组织修复，但其失调会损害子宫内膜功能。这种调节的核心是p53、AMPK和mTOR，它们协调应激反应、代谢调节和增殖控制。p53激活AMPK并抑制mTOR，促进能量保存并限制衰老。AMPK也抑制mTOR，减少与年龄相关的功能障碍。这个p53-AMPK-mTOR轴以及自噬，根据应激和营养状况来决定细胞命运。虽然适度的衰老支持子宫内膜功能，但过度积累会阻碍生育能力。了解这些分子相互作用可能会推进生育治疗以及对抗生殖衰老的策略。
