Core Viewpoint - The study identifies ribosome dysregulation as a potential causal mechanism driving female reproductive aging, particularly highlighting the upregulation of ribosomal gene transcription in oocytes and cumulus cells around the age of 34, which correlates with a decline in fertility. It suggests that short-term intervention with rapamycin may serve as an effective treatment for age-related infertility [2][11]. Group 1: Mechanisms of Female Reproductive Aging - Female fertility declines with age, especially after 35, primarily due to decreased oocyte quality, which affects embryo development and leads to repeated failures in assisted reproduction [2][4]. - Chromosomal segregation errors increase with age, particularly after 35, contributing to aneuploidy in embryos, which often results in developmental arrest or miscarriage [4]. - Other factors contributing to ovarian aging include DNA damage response, oxidative stress, mitochondrial dysfunction, telomere shortening, autophagy, inflammation, and fibrosis [5]. Group 2: Molecular Changes in Oocytes and Cumulus Cells - The study utilized multi-omics analysis to discover molecular changes in aging oocytes and cumulus cells, revealing significant transcriptional alterations at age 34, including upregulation of ribosomal gene transcription [8][9]. - The research indicates that specific genomic loci exhibit DNA hypomethylation and abnormal heterochromatin deposition, closely associated with the activation of ribosomal gene transcription [8][9]. - The abundance of histone H3K9me3 decreases with age, which is linked to the upregulation of ribosomal genes [9]. Group 3: Implications for Treatment - Short-term treatment with the clinically approved immunosuppressant rapamycin can effectively inhibit protein translation in cumulus cells and restore protein homeostasis, leading to improved embryo quality and higher rates of pregnancy and live births [9][11].