《生命科学》 2026, 38(6): 981-1003
卵巢衰老：女性系统性衰老的调控中枢与驱动机制
摘 要：
卵巢是女性最早发生功能衰退的器官之一，其衰老不仅标志着生育力下降，更可能构成女性系统性衰老的关键转折节点。目前，卵巢衰老的细胞与分子基础，以及其作为衰老信号源向全身多器官播散的具体路径，仍缺乏系统性的整合研究。本文围绕“卵巢衰老是否驱动女性系统性衰老”这一基础性科学问题，从卵巢细胞网络、分子通路与内分泌重塑层面进行系统梳理。在细胞层面，卵母细胞与卵巢多种类型体细胞在衰老过程中发生结构与功能重构，导致卵巢微环境稳态失衡。在分子层面，基因组不稳定、表观遗传重编程、蛋白质稳态破坏、线粒体功能衰退及代谢重塑等核心事件通过信号通路的交叉对话形成复杂的调控网络，共同促进慢性炎症微环境形成、组织纤维化进展以及细胞间通讯功能的渐进性紊乱。衰老卵巢能通过内分泌重塑、衰老相关分泌表型诱导的炎症扩散以及外泌体信号传递等多重通路，将局部衰老信号放大并传播至远端器官，加速心血管、骨骼、神经及代谢系统的功能退化。基于机体组织器官衰老时间顺序以及相关因果推断证据，本文提出卵巢衰老和卵巢早衰是连接生殖衰老与机体多系统衰老的关键因素。深入解析卵巢衰老的细胞与分子机制及其系统性效应，将为延缓女性生殖衰老、干预多器官协同衰老并促进全生命周期健康提供新的理论基础与潜在干预靶点。
通讯作者：朱正茂 , Email:zhuzhengmao@nankai.edu.cn 刘 林 , Email:liulin@nankai.edu.cn
Abstract:
Ovarian aging occurs significantly earlier than the overt aging of most somatic organs, indicating that it is not merely a passive consequence of systemic aging but a potential upstream regulator of female organismal decline. This review aims to comprehensively synthesize current evidence on the cellular, molecular, and systemic mechanisms underlying ovarian aging, to clarify how intra-ovarian changes reshape intercellular communication networks, and to elucidate how ovary-derived signals contribute to aging in distant organs. The ovary is a unique organ integrating reproductive and endocrine functions, maintaining a finite follicular reserve while secreting hormones such as estrogen, inhibin, anti-Müllerian hormone, and diverse bioactive factors. Unlike most somatic tissues, ovarian aging begins early, with a marked decline in ovarian reserve typically observed in women in their early thirties. Emerging single-cell and multi-omics studies reveal that ovarian aging is a dynamic, multicellular process involving coordinated dysfunction across oocytes, granulosa cells, theca cells, endothelial cells, stromal cells, immune cells, and neuro-glial networks. These cell types exhibit distinct yet interconnected aging phenotypes, including altered differentiation trajectories, inflammatory activation, fibrosis, and impaired vascular and metabolic support. At the molecular level, four convergent hallmarks dominate: genomic instability, epigenetic and transcriptional reprogramming, loss of proteostasis, and energy metabolic dysfunction. These mechanisms interact to create a self-reinforcing microenvironment characterized by oxidative stress, inflammation, hypoxia, and extracellular matrix remodeling. Critically, ovarian aging disrupts key intra-follicular communication systems—metabolic coupling, paracrine signaling, and steroidogenesis—leading to progressive follicular failure. Beyond the ovary, aging-related endocrine changes, senescence-associated secretory phenotype, and extracellular vesicles act systemically, promoting cardiovascular disease, osteoporosis, neurodegeneration, and metabolic disorders. Both clinical and experimental evidence supports a causal role, with timing-dependent effects observed in interventions such as hormone replacement therapy. We propose that ovarian aging functions as a central regulatory hub in female systemic aging. Future research should focus on high-resolution spatial multi-omics, computational modeling of intercellular networks, and development of human-relevant models such as ovarian organoids. Identifying critical transition points and early biomarkers will be essential for designing precise, time-sensitive interventions aimed at preserving ovarian function
and extending female healthspan.
Communication Author：ZHU Zheng-Mao , Email:zhuzhengmao@nankai.edu.cn LIU Lin , Email:liulin@nankai.edu.cn
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