Insights into lower reproductive tract aging: Mechanisms and perspectives

Rising global life expectancy intensifies the health impact of female lower reproductive tract aging, particularly affecting the uterus, cervix, and vagina. This process is primarily driven by estrogen depletion triggering hormonal imbalance, chronic inflammation, cellular senescence through senescence-associated secretory phenotype mediators, and systemic oxidative stress. These interconnected mechanisms accelerate structural degeneration leading to uterine fibrosis with endometrial atrophy, pelvic organ prolapse, cervical susceptibility to persistent HPV infections and subsequent malignancy development, vaginal microbiome disruption, and genitourinary syndrome of menopause. Future advances will require addressing the pronounced research imbalance across anatomical sites, resolving the causal links between immune aging and tissue-specific pathologies, and integrating multi-omics and organoid technologies to enable personalized, site-specific interventions.