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The traditional concept of the \u201cage gap (AG),\u201d defined as the difference between estimated biological age and an individual's chronological age, has been used for self\u2010monitoring the risk of age\u2010related diseases. However, the current AG does not account for the stratified aging patterns across different stages of chronological age, which may lead to biased or paradoxical interpretations of aging acceleration. To address these limitations, we propose Personalized\u2010context\u2010Aware Age Gap (PAAG), a robust metric to estimate aging acceleration, based on our new pre\u2010training model AOE\u2010Net (Age Order Enhanced Network). AOE\u2010Net employs age\u2010order enhanced contrastive learning on multi\u2010omics data from healthy populations to learn latent representations that accurately reconstruct aging trajectories by capturing biological deviation rather than technical deviation in omics data. We demonstrate that PAAG, generated via fine\u2010tuning AOE\u2010Net, significantly outperforms AG of conventional first\u2010 and second\u2010generation aging clocks in predicting clinical outcomes. This superior predictive power was validated across diverse age\u2010related diseases and phenotypes: pan\u2010cancer (overall survival), subclinical atherosclerosis (PESA score), and osteoporosis (bone mineral density). Crucially, PAAG serves as a context\u2010aware metric that may improve the clinical outcome prediction of existing aging clocks. Furthermore, interpretive analysis of PAAG's molecular drivers revealed a strong functional enrichment for immune\u2010response pathways, providing a shared mechanistic link between accelerated aging and disease. Collectively, PAAG could serve as a stable indicator of aging acceleration for clinically assessing age\u2010related diseases, and AOE\u2010Net provides an effective pre\u2010training model for aging study and PAAG evaluation.<\/jats:p>","DOI":"10.1111\/acel.70552","type":"journal-article","created":{"date-parts":[[2026,5,29]],"date-time":"2026-05-29T06:22:16Z","timestamp":1780035736000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Personalized\u2010Context\u2010Aware Age Gap: A New Multi\u2010Omics Measurement Based on Age\u2010Enhanced Model\n                    <scp>AOE<\/scp>\n                    \u2010Net for Aging Acceleration and Chronic Disease Risk Prediction"],"prefix":"10.1111","volume":"25","author":[{"given":"Feng\u2010Ao","family":"Wang","sequence":"first","affiliation":[{"name":"Bioland Laboratory  Guangzhou China"},{"name":"Key Laboratory of Systems Health Science of Zhejiang Province, School of Life Science, Hangzhou Institute for Advanced Study University of Chinese Academy of Sciences  Hangzhou China"},{"name":"Guangzhou National Laboratory  Guangzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tao","family":"Zeng","sequence":"additional","affiliation":[{"name":"Bioland Laboratory  Guangzhou China"},{"name":"Guangzhou National Laboratory  Guangzhou China"},{"name":"GMU\u2010GIBH Joint School of Life Sciences, Guangdong Provincial Key Laboratory of Protein Modification and Disease, The Guangdong\u2010Hong Kong\u2010Macao Joint Laboratory for Cell Fate Regulation and Diseases Guangzhou Medical University  Guangzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4314-4990","authenticated-orcid":false,"given":"Chunchun","family":"Yuan","sequence":"additional","affiliation":[{"name":"Longhua Hospital Shanghai University of Traditional Chinese Medicine  Shanghai China"},{"name":"Key Laboratory of Theory and Therapy of Muscles and Bones Ministry of Education  Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hongyu","family":"Wang","sequence":"additional","affiliation":[{"name":"Longhua Hospital Shanghai University of Traditional Chinese Medicine  Shanghai China"},{"name":"Key Laboratory of Theory and Therapy of Muscles and Bones Ministry of Education  Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yule","family":"Yu","sequence":"additional","affiliation":[{"name":"Key Laboratory of Systems Health Science of Zhejiang Province, School of Life Science, Hangzhou Institute for Advanced Study University of Chinese Academy of Sciences  Hangzhou China"},{"name":"Guangzhou National Laboratory  Guangzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Enjin","family":"Deng","sequence":"additional","affiliation":[{"name":"Guangzhou National Laboratory  Guangzhou China"},{"name":"College of Animal Science and Technology Guangxi University  Nanning China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yao","family":"Wang","sequence":"additional","affiliation":[{"name":"Key Laboratory of Systems Health Science of Zhejiang Province, School of Life Science, Hangzhou Institute for Advanced Study University of Chinese Academy of Sciences  Hangzhou China"},{"name":"Guangzhou National Laboratory  Guangzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiangxun","family":"Ji","sequence":"additional","affiliation":[{"name":"Longhua Hospital Shanghai University of Traditional Chinese Medicine  Shanghai China"},{"name":"Key Laboratory of Theory and Therapy of Muscles and Bones Ministry of Education  Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiarui","family":"Cui","sequence":"additional","affiliation":[{"name":"Longhua Hospital Shanghai University of Traditional Chinese Medicine  Shanghai China"},{"name":"Key Laboratory of Theory and Therapy of Muscles and Bones Ministry of Education  Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dezhi","family":"Tang","sequence":"additional","affiliation":[{"name":"Longhua Hospital Shanghai University of Traditional Chinese Medicine  Shanghai China"},{"name":"Key Laboratory of Theory and Therapy of Muscles and Bones Ministry of Education  Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2292-8884","authenticated-orcid":false,"given":"Ruikun","family":"He","sequence":"additional","affiliation":[{"name":"BYHEALTH Institute of Nutrition &amp; 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