{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,16]],"date-time":"2026-09-16T07:55:54Z","timestamp":1789545354237,"version":"build-2803163510"},"reference-count":193,"publisher":"MDPI AG","issue":"12","license":[{"start":{"date-parts":[[2025,6,6]],"date-time":"2025-06-06T00:00:00Z","timestamp":1749168000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cells"],"abstract":"<jats:p>The endometrium is essential for reproductive function, supporting implantation and pregnancy through mechanisms such as hormonal responsiveness, immune regulation, and tissue regeneration. Aging disrupts these processes, with cellular senescence\u2014marked by irreversible cell cycle arrest due to DNA damage and oxidative stress\u2014being a key contributor. While senescence aids in tumor suppression and tissue repair, its dysregulation impairs endometrial function. Central to this regulation are p53, AMPK, and mTOR, which coordinate stress responses, metabolic regulation, and proliferation control. p53 activates AMPK and inhibits mTOR, promoting energy conservation and limiting senescence. AMPK also suppresses mTOR, reducing age-related dysfunction. This p53\u2013AMPK\u2013mTOR axis, along with autophagy, governs cell fate in response to stress and nutrient status. Although moderate senescence supports endometrial function, excessive accumulation can hinder fertility. Understanding these molecular interactions may advance fertility treatments and strategies to counteract reproductive aging.<\/jats:p>","DOI":"10.3390\/cells14120858","type":"journal-article","created":{"date-parts":[[2025,6,6]],"date-time":"2025-06-06T11:08:31Z","timestamp":1749208111000},"page":"858","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":14,"title":["Molecular Mechanisms of Cellular Senescence in Age-Related Endometrial Dysfunction"],"prefix":"10.3390","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8124-6269","authenticated-orcid":false,"given":"Hiroshi","family":"Kobayashi","sequence":"first","affiliation":[{"name":"Department of Gynecology and Reproductive Medicine, Ms.Clinic MayOne, 871-1 Shijo-cho, Kashihara 634-0813, Japan"},{"name":"Department of Obstetrics and Gynecology, Nara Medical University, 840 Shijo-cho, Kashihara 634-8522, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mai","family":"Umetani","sequence":"additional","affiliation":[{"name":"Department of Gynecology and Reproductive Medicine, Ms.Clinic MayOne, 871-1 Shijo-cho, Kashihara 634-0813, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Miki","family":"Nishio","sequence":"additional","affiliation":[{"name":"Department of Gynecology and Reproductive Medicine, Ms.Clinic MayOne, 871-1 Shijo-cho, Kashihara 634-0813, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hiroshi","family":"Shigetomi","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology, Nara Medical University, 840 Shijo-cho, Kashihara 634-8522, Japan"},{"name":"Department of Gynecology and Reproductive Medicine, Aska Ladies Clinic, 3-3-17 Kitatomigaoka-cho, Nara 634-0001, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shogo","family":"Imanaka","sequence":"additional","affiliation":[{"name":"Department of Gynecology and Reproductive Medicine, Ms.Clinic MayOne, 871-1 Shijo-cho, Kashihara 634-0813, Japan"},{"name":"Department of Obstetrics and Gynecology, Nara Medical University, 840 Shijo-cho, Kashihara 634-8522, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hiratsugu","family":"Hashimoto","sequence":"additional","affiliation":[{"name":"Department of Gynecology and Reproductive Medicine, Ms.Clinic MayOne, 871-1 Shijo-cho, Kashihara 634-0813, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,6,6]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"63","DOI":"10.1111\/j.1600-0897.2011.01034.x","article-title":"Innate immunity in the human endometrium and ovary","volume":"66","author":"Sheldon","year":"2011","journal-title":"Am. 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