{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,21]],"date-time":"2026-10-21T19:44:34Z","timestamp":1792611874800,"version":"4.5.0"},"reference-count":61,"publisher":"Wiley","issue":"10","license":[{"start":{"date-parts":[[2026,10,18]],"date-time":"2026-10-18T00:00:00Z","timestamp":1792281600000},"content-version":"vor","delay-in-days":17,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T00:00:00Z","timestamp":1790812800000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100012166","name":"National Key Research and Development Program of China","doi-asserted-by":"publisher","award":["2024YFC2510805"],"award-info":[{"award-number":["2024YFC2510805"]}],"id":[{"id":"10.13039\/501100012166","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Aging Cell"],"published-print":{"date-parts":[[2026,10]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    Maintaining health during global population aging represents a critical challenge, where mosaic loss of chromosome Y (LOY) in the hematopoietic system surfaces as a prevalent somatic mutation in aging men. However, its longitudinal impact on sensory organ degeneration remains insufficiently characterized. Analyzing 223,051 male participants from the UK Biobank, we demonstrated that LOY uniquely and independently predicted an increased risk of incident age\u2010related macular degeneration (AMD) (Hazard Ratio\u2009=\u20090.611, 95% Confidence Interval: 0.397\u20130.942). Restricted cubic splines identified a critical risk escalation threshold at \u22120.17 for median log R ratio. Over a 15\u2010year preclinical window, Olink plasma proteomics identified 41 prioritized proteins demonstrating divergent nonlinear kinetic profiles leading up to clinical diagnosis; notably, the elastin\u2010degrading matrix metalloproteinase\u201012 deviated significantly 12\u2009years prior to endpoint. Integrating single\u2010cell RNA sequencing datasets of peripheral blood and choroidal tissues validated that CD16\n                    <jats:sup>+<\/jats:sup>\n                    circulatory monocytes and resident macrophages exhibited peak LOY frequencies. Furthermore, Y\u2010deficient myeloid cells manifested a pro\u2010inflammatory phenotype with cell\u2010type\u2010specific upregulation of\n                    <jats:italic>IFI30<\/jats:italic>\n                    and\n                    <jats:italic>CKB<\/jats:italic>\n                    , bridging single\u2010cell transcriptional activation with systemic proteomic dysregulation. Causal mediation analysis confirmed that peripheral monocyte counts significantly mediated the LOY\u2010associated degenerative risk. Utilizing these prioritized proteomic signatures, a LightGBM machine learning framework achieved robust predictive performance for 5\u2010year incident risk (AUC\u2009=\u20090.734). Collectively, these findings establish a distinct somatic mutation\u2010immune\u2010retinal axis, positioning systemic clonal mosaicism not merely as a marker of biological senescence but as an upstream driver of site\u2010specific organ degeneration, offering novel strategies for early risk stratification and precision intervention in aging\u2010related diseases.\n                  <\/jats:p>","DOI":"10.1111\/acel.70775","type":"journal-article","created":{"date-parts":[[2026,10,19]],"date-time":"2026-10-19T03:04:30Z","timestamp":1792379070000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Systemic Loss of Chromosome Y Associates With Age\u2010Related Ophthalmic Diseases in Middle\u2010Aged Men: A Longitudinal Multi\u2010Omic Study"],"prefix":"10.1111","volume":"25","author":[{"given":"Tianhao","family":"Chen","sequence":"first","affiliation":[{"name":"Eye Institute and Department of Ophthalmology Eye &amp; ENT Hospital, Fudan University  Shanghai China"},{"name":"NHC Key Laboratory of Myopia and Related Eye Diseases Chinese Academy of Medical Sciences  Shanghai China"},{"name":"Shanghai Research Center of Ophthalmology and Optometry Eye &amp; 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