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HP experiments demonstrated that systemic factors from young mice rejuvenated aged retinas and alleviated senescent phenotypes, while aged blood accelerated aging in young mice. Integrative analysis pinpointed adiponectin receptor 1 (AdipoR1) and the downstream adenosine 5\u2032-monophosphate\u2013activated protein kinase (AMPK) signaling pathway as central to the molecular mechanisms underlying retinal rejuvenation. Treatment with the AdipoR1 agonist AdipoRon reversed retinal aging. Mechanistically, AdipoR1-AMPK activation promoted mitochondrial function, contributing to the restoration of youthful cellular phenotypes. Together, our study identifies AdipoR1 as a therapeutic target for retinal aging and provides insights into the molecular programs driving retinal rejuvenation.<\/jats:p>","DOI":"10.1126\/sciadv.adv6642","type":"journal-article","created":{"date-parts":[[2025,7,16]],"date-time":"2025-07-16T18:00:36Z","timestamp":1752688836000},"update-policy":"https:\/\/doi.org\/10.34133\/aaas_crossmark","source":"Crossref","is-referenced-by-count":5,"title":["Heterochronic parabiosis uncovers AdipoR1 as a critical player in retinal rejuvenation"],"prefix":"10.1126","volume":"11","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8112-6662","authenticated-orcid":true,"given":"Yidan","family":"Liu","sequence":"first","affiliation":[{"name":"State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Guangdong Provincial Key Laboratory of Ophthalmology and Visual Science, Sun Yat-sen University, Guangzhou 510060, 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