Ovarian aging at single-cell resolution: Current paradigms and perspectives

Ovarian failure is a key event in female reproductive aging, resulting in the depletion of follicular reserve and a decline in fertility. In addition, it triggers systemic pathological changes, including osteoporosis and cardiovascular disease, due to decreased estrogen levels. Despite extensive study, mapping senescent ovarian cells is challenging due to the multicellular composition and heterogeneity of the ovary. In the past decade, single-cell resolution technologies have provided new insights into ovarian aging by enabling the molecular characterization of individual cells. Here, we comprehensively review the application of these technologies in delaying ovarian aging and promoting reproductive health. We summarize their value in uncovering cell-type-specific mechanisms and their potential uses in the research of ovarian aging, ultimately deepening our understanding of its pathogenesis and molecular basis.