2026-10-14T22:53:19Z https://www.scidb.cn/oai

10.57760/sciencedb.38438 2026-06-08T14:38:16Z

2026-06-08 Ovarian failure drives systemic aging at single-cell resolution doi:10.57760/sciencedb.38438 en The aging of the female reproductive system, particularly the decline in ovarian function or premature ovarian insufficiency (POI), is closely associated with an increased risk of numerous age-related diseases. Yet, the molecular pathways underlying the somatic aging driven by ovarian failure remain largely unexplored. We report that ovarian failure promotes systemic aging across multiple organs. Furthermore, we show that POI triggers aging-associated transcriptional programs characterized by mitochondrial dysfunction, metabolic dysregulation, chronic inflammation, fibrosis and stem cell depletion. These changes are underpinned by sustained activation of cAMP signaling and suppression of PPAR-dependent metabolic pathways. Moreover, compared with estrogen replacement alone, ovarian transplantation restored systemic functions, particularly stem cell function, and reversed transcriptional aging signatures more broadly, indicating that ovarian function governs somatic organ aging beyond estrogen. Pharmacological modulation of cAMP or PPAR attenuates POI-associated cellular senescence. These findings provide molecular insights into the role of the ovary as an active regulator of organismal aging and may have clinical implications for mitigating aging-related decline following ovarian failure. Premature ovarian insufficiency; aging; cAMP-PPAR axis; Single-cell transcriptomics; Ovarian transplantation Lin Liu RESTRICTED dataset Science Data Bank