New advances in research on amino acid metabolism regulation in ovarian aging

doi:10.11958/20252509

Abstract

Abstract:

The core characteristics of ovarian aging are the depletion of ovarian follicle reserve and the decline in oocyte quality. In recent years, disordered amino acid metabolism has been confirmed to be closely associated with the process of ovarian aging. This article provides a systematic review of the role of amino acid metabolic network in ovarian aging. It encompasses various aging-related metabolic alterations, including dysregulated branched-chain amino acid (BCAA) metabolism, increased glutamine dependency coupled with reduced metabolic efficiency, impaired one-carbon metabolism, disturbances in the arginine-nitric oxide-polyamine axis and changes in taurine levels. These metabolic changes impair follicular development, granulosa cell function and oocyte quality through multiple mechanisms. This review not only offers a new perspective for understanding the pathological mechanisms of ovarian aging but also provides a crucial theoretical foundation for developing innovative strategies—such as nutritional interventions or targeted regulation of amino acid metabolism—to delay ovarian aging and improve female fertility potential.

Key words: ovary, aging, oocytes, amino acids, epigenomics, granulosa cells, amino acid metabolism

CLC Number:

Figures/Tables 1

References 52

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代谢通路/机制	关键氨基酸	生理作用	与卵巢衰老的关联	潜在干预方向
蛋白质合成与修复^[11]	所有必需氨基酸	维持卵巢细胞结构完整性；支持激素合成与分泌	合成不足→细胞功能衰退、激素失衡；修复障碍→损伤累积	保证优质蛋白摄入；优化氨基酸比例
能量供应^[12]	BCAAs；Gln	通过糖异生/三羧酸循环（TCA）循环供能；支持卵泡发育与卵母细胞成熟	代谢效率下降→卵巢能量受限；线粒体功能障碍→卵子质量降低	改善线粒体功能；调节BCAAs平衡
抗氧化^[13]	含硫氨基酸（蛋氨酸/半胱氨酸）；甘氨酸/丝氨酸	合成GSH；清除活性氧（ROS）	GSH减少→氧化损伤累积；DNA/蛋白质损伤→卵泡闭锁加速；卵母细胞质量下降	补充N-乙酰半胱氨酸（NAC）；增强抗氧化
mTORC1信号通路^[14]	亮氨酸（最强激活剂）	调节细胞生长、增殖与自噬	慢性激活→抑制自噬；卵泡过度激活与耗竭；炎症反应增加→加速OR下降	mTOR抑制剂（如雷帕霉素）；限制亮氨酸过量
通用控制非阻遏蛋白2 （GCN2）应激通路^[15]	所有氨基酸（缺乏时激活）	应对营养压力；抑制非必需蛋白合成	持续激活→代谢失衡标志，损害细胞功能	维持氨基酸稳态；避免长期营养不良
一碳代谢^[16]	甘氨酸/丝氨酸/蛋氨酸	提供甲基基团；支持DNA合成/修复；调控表观遗传	一碳代谢障碍→同型半胱氨酸升高；DNA损伤累积；基因表达异常→加速卵巢衰老	补充叶酸/B族维生素；优化甲基供体
微环境调节^[17]	Arg	合成一氧化氮（NO）与多胺；调节卵巢血流与激素分泌	NO减少→血流灌注不足；颗粒细胞-卵母细胞通讯异常→卵泡发育障碍	Arg补充；改善血管功能
神经内分泌调节^[18]	色氨酸/酪氨酸	合成血清素/多巴胺前体；影响下丘脑-垂体-卵巢轴功能	代谢紊乱→生殖激素分泌失调；排卵障碍/周期紊乱	平衡膳食摄入；管理应激反应

代谢通路/机制	关键氨基酸	生理作用	与卵巢衰老的关联	潜在干预方向
蛋白质合成与修复^[11]	所有必需氨基酸	维持卵巢细胞结构完整性；支持激素合成与分泌	合成不足→细胞功能衰退、激素失衡；修复障碍→损伤累积	保证优质蛋白摄入；优化氨基酸比例
能量供应^[12]	BCAAs；Gln	通过糖异生/三羧酸循环（TCA）循环供能；支持卵泡发育与卵母细胞成熟	代谢效率下降→卵巢能量受限；线粒体功能障碍→卵子质量降低	改善线粒体功能；调节BCAAs平衡
抗氧化^[13]	含硫氨基酸（蛋氨酸/半胱氨酸）；甘氨酸/丝氨酸	合成GSH；清除活性氧（ROS）	GSH减少→氧化损伤累积；DNA/蛋白质损伤→卵泡闭锁加速；卵母细胞质量下降	补充N-乙酰半胱氨酸（NAC）；增强抗氧化
mTORC1信号通路^[14]	亮氨酸（最强激活剂）	调节细胞生长、增殖与自噬	慢性激活→抑制自噬；卵泡过度激活与耗竭；炎症反应增加→加速OR下降	mTOR抑制剂（如雷帕霉素）；限制亮氨酸过量
通用控制非阻遏蛋白2 （GCN2）应激通路^[15]	所有氨基酸（缺乏时激活）	应对营养压力；抑制非必需蛋白合成	持续激活→代谢失衡标志，损害细胞功能	维持氨基酸稳态；避免长期营养不良
一碳代谢^[16]	甘氨酸/丝氨酸/蛋氨酸	提供甲基基团；支持DNA合成/修复；调控表观遗传	一碳代谢障碍→同型半胱氨酸升高；DNA损伤累积；基因表达异常→加速卵巢衰老	补充叶酸/B族维生素；优化甲基供体
微环境调节^[17]	Arg	合成一氧化氮（NO）与多胺；调节卵巢血流与激素分泌	NO减少→血流灌注不足；颗粒细胞-卵母细胞通讯异常→卵泡发育障碍	Arg补充；改善血管功能
神经内分泌调节^[18]	色氨酸/酪氨酸	合成血清素/多巴胺前体；影响下丘脑-垂体-卵巢轴功能	代谢紊乱→生殖激素分泌失调；排卵障碍/周期紊乱	平衡膳食摄入；管理应激反应