Oocyte Aging as a Systems-Level Failure of Cellular Quality Control Networks: Insights from Comparative Biology.

Oocyte aging is a conserved biological process that limits reproductive success across animal taxa. While most research has focused on mammalian systems, particularly humans, comparative studies reveal both shared molecular mechanisms and lineage-specific adaptations that shape oocyte longevity. Here, we synthesise current knowledge on chromosomal instability, mitochondrial dysfunction, proteostasis collapse and epigenetic alterations, integrating insights from insects, nematodes and vertebrates. We argue that these phenomena should not be viewed as independent hallmarks of reproductive aging but rather as interconnected manifestations of a progressive decline in cellular quality control networks. By comparing taxa, we identify both conserved vulnerabilities, including cohesin loss, mitochondrial deterioration and genome instability, and lineage-specific adaptations that mitigate their effects. We further propose the hypothesis that biomolecular condensates, including the Balbiani body, nuage and recently described endolysosomal assemblies, may function as higher-order organizational hubs coordinating mitochondrial quality control, proteostasis and genome defence. This perspective provides a unifying framework for understanding oocyte aging as a systems-level process and highlights new directions for future studies of reproductive longevity.