Ovarian aging and systemic health: Mechanisms and emerging intervention strategies.
Ovarian aging may contribute to systemic aging via the ovarian-systemic axis. This review outlines intrinsic ovarian cellular defects such as genomic instability, epigenetic shifts, and mitochondrial and proteostasis damage, which may trigger senescence-associated secretory phenotype (SASP)-related inflammaging, fibrosis, and distal pro-aging signals. Ovarian-derived endocrine disruption, especially estrogen decline, broadly affects bodily physiology. We summarize emerging multimodal interventions, including senolytics, metabolic reprogramming, regenerative medicine, and systemic approaches, and we discuss their dual potential to preserve fertility and intercept ovarian contributions to systemic aging. Ovarian aging is possibly associated with female age-related multimorbidity. Ovary-targeted prevention may extend healthspan, as assessed by combined reproductive and systemic clinical evaluations.