{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,19]],"date-time":"2026-09-19T17:45:33Z","timestamp":1789839933646,"version":"4.0.1"},"reference-count":128,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,2,24]],"date-time":"2026-02-24T00:00:00Z","timestamp":1771891200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Cell Dev. Biol."],"abstract":"<jats:p>Premature ovarian insufficiency (POI) is more than a fertility issue; it's a silent epidemic of accelerated systemic aging in young women, with current treatments failing to address its root cause. For too long, the relentless decline of ovarian function has been viewed as an inevitable mystery. But what if the ovary holds an internal \u201cinflammatory clock,\u201d ticking away with each cellular insult and dictating the pace of its own decline? Here, we spotlight a surprising culprit: the cGAS-STING signaling pathway. Far beyond its day job in antiviral defense, this pathway emerges as a master integrator of ovarian aging. We reveal how stresses like DNA damage and mitochondrial dysfunction leak genetic material into the cell\u2019s interior, where cGAS-STING sounds a relentless alarm. This alarm does not just trigger inflammation; it initiates a vicious, self-amplifying cycle of cellular senescence, tissue fibrosis, and follicle destruction\u2014a cycle that may explain why ovarian aging often feels like a one-way street. Therapeutically, we move beyond mere symptom management to explore strategies for resetting this inflammatory clock. We dissect both direct \u201cbrakes\u201d\u2014novel small molecules that silence cGAS or STING\u2014and upstream \u201cshields\u201d that protect cellular powerplants and genome integrity. Most provocatively, we introduce the concept of \u201csignal reprogramming\u201d: not just shutting down the pathway, but cleverly rewiring its output to favor repair over destruction. By repositioning cGAS-STING from a simple sensor to the central processor of ovarian aging, this review charts a course for a new class of therapeutics aimed at preserving ovarian function, not just managing its loss. The goal is no less than transforming our approach to women\u2019s reproductive longevity.<\/jats:p>","DOI":"10.3389\/fcell.2026.1771546","type":"journal-article","created":{"date-parts":[[2026,2,24]],"date-time":"2026-02-24T09:56:14Z","timestamp":1771926974000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":6,"title":["The inflammatory clock: how cGAS-STING ticks in the aging ovary"],"prefix":"10.3389","volume":"14","author":[{"given":"Yanjing","family":"Ma","sequence":"first","affiliation":[{"name":"Department of Gynecology, Wuxi Maternal and Child Health Hospital, Wuxi School of Medicine, Jiangnan University","place":["Wuxi, Jiangsu, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yu","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Gynecology, Wuxi Maternal and Child Health Hospital, Wuxi School of Medicine, Jiangnan University","place":["Wuxi, Jiangsu, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiong","family":"Yuan","sequence":"additional","affiliation":[{"name":"Department of Gynecology, Wuxi Maternal and Child Health Hospital","place":["Wuxi, Jiangsu, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tingyu","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Gynecology, Wuxi Maternal and Child Health Hospital, Wuxi School of Medicine, Jiangnan University","place":["Wuxi, Jiangsu, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hao","family":"Luo","sequence":"additional","affiliation":[{"name":"Department of Gynecology, Wuxi Maternal and Child Health Hospital, Wuxi School of Medicine, Jiangnan University","place":["Wuxi, Jiangsu, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yanfang","family":"Gu","sequence":"additional","affiliation":[{"name":"Department of Gynecology, Wuxi Maternal and Child Health Hospital, Wuxi School of Medicine, Jiangnan University","place":["Wuxi, Jiangsu, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,2,24]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"5403","DOI":"10.1038\/s41467-024-49460-1","article-title":"IFN\u03b3 causes mitochondrial dysfunction and oxidative stress in myositis","volume":"15","author":"Abad","year":"2024","journal-title":"Nat. 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