Decoding ovarian aging in women: Cellular damage, signaling networks, and treatment frontiers

Abstract

Ovarian aging is a significant biological process characterized by the gradual decline of ovarian function and fertility in women as they age. It is a multifaceted process that involves various molecular mechanisms. This review article delves into the complex nature of ovarian aging, marked by reductions in both the quantity and quality of oocytes, hormonal imbalances, and heightened risks of infertility and pregnancy complications. It consolidates current understanding of the physiological, cellular, and molecular mechanisms driving ovarian aging, such as mitochondrial dysfunction, oxidative stress, telomere shortening, DNA (Deoxyribonucleic Acid) damage, inflammation, and apoptosis. This review primarily focuses on human ovarian aging, while also integrating relevant insights from animal models particularly rodent studies that have contributed to our understanding of underlying mechanisms. It explores key signaling pathways involved in aging, including AMPK (AMP-Activated Protein Kinase), mTOR (mammalian target of rapamycin), Nrf2 (Nuclear Factor Erythroid 2-Related Factor 2), SIRT1 (Sirtuin 1), and FOXO3 (Forkhead Box O Transcription Factor) pathways. The review also discusses emerging therapeutic strategies designed to delay or reverse ovarian aging, which include antioxidants, hormone replacement therapy, stem cell-based treatments, CRMs (CR mimetics), gene therapy, and traditional medicines. Additionally, the article examines the potential role of polyamines in ovarian function and aging. By thoroughly analyzing the current research landscape and identifying future research directions, this review offers valuable insights for researchers and clinicians dedicated to improving reproductive health and quality of life for aging women.