Animal models in ovarian aging research – an updated review

Ovarian aging represents a multifactorial biological process characterized by progressive depletion of the follicular reserve, endocrine dysregulation, mitochondrial dysfunction, genomic instability, stromal remodeling, and chronic inflammation. While clinical studies in women provide essential insights, mechanistic dissection of ovarian senescence depends largely on animal models. This review presents a comparative and evolutionary synthesis of ovarian aging across invertebrate and vertebrate species, from Caenorhabditis elegans and Drosophila melanogaster to rodents, livestock, equine, and non-human primate models. We integrate conserved and divergent mechanisms, including telomere dynamics, oxidative stress, DNA damage repair, fibrosis, metabolic decline, immune activation, and endocrine transitions. We critically evaluate translational relevance, genetic manipulability, physiological similarity to humans, and suitability for longitudinal and interventional studies. Finally, we discuss emerging alternatives such as ovarian organoids, ovary-on-chip systems, and cross-species single-cell omics approaches. This integrative framework aims to guide rational model selection for mechanistic, translational, and therapeutic research in ovarian aging.