Mechanistic insights into aging and longevity: Implications for ovarian function and health

Ovarian aging is characterized by progressive follicular reserve depletion, mitochondrial dysfunction, oxidative stress, and endocrine decline. This review examines the molecular mechanisms driving ovarian aging and evaluates emerging therapeutic strategies to preserve reproductive longevity. Key mechanistic contributors include telomere attrition, accumulated DNA damage, impaired autophagy, chronic inflammation, and dysregulation of major longevity pathways such as PI3K/AKT/mTOR, AMPK, and sirtuins. Disruption of these interconnected signaling networks accelerates follicular activation, granulosa cell apoptosis, and oocyte quality decline. We further discuss targeted interventions aimed at modulating these pathways, including mTOR inhibitors, AMPK activators, antioxidants, mitochondrial protectants, autophagy regulators, and select nutraceuticals. Compounds such as rapamycin, metformin, resveratrol, and melatonin demonstrate mechanistic promise in preclinical and emerging clinical studies. Nutritional and lifestyle modifications may complement pharmacological approaches. Collectively, advancing mechanistic understanding of ovarian aging provides a foundation for developing precision strategies to delay menopause, preserve fertility, and improve women's healthspan.