{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,21]],"date-time":"2026-08-21T14:46:30Z","timestamp":1787323590499,"version":"build-2736575974"},"reference-count":43,"publisher":"Wiley","issue":"8","license":[{"start":{"date-parts":[[2026,7,25]],"date-time":"2026-07-25T00:00:00Z","timestamp":1784937600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,7,25]],"date-time":"2026-07-25T00:00:00Z","timestamp":1784937600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100018542","name":"Natural Science Foundation of Sichuan Province","doi-asserted-by":"publisher","award":["2025ZNSFSC1775"],"award-info":[{"award-number":["2025ZNSFSC1775"]}],"id":[{"id":"10.13039\/501100018542","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100032767","name":"Sichuan Medical Association","doi-asserted-by":"publisher","award":["S21003"],"award-info":[{"award-number":["S21003"]}],"id":[{"id":"10.13039\/100032767","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82171584"],"award-info":[{"award-number":["82171584"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["72374180"],"award-info":[{"award-number":["72374180"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Aging Cell"],"published-print":{"date-parts":[[2026,8]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    The musculoskeletal system is key to aging. Nonetheless, existing protein\u2010based musculoskeletal aging clocks have limited predictive performance and fail to characterize genetic or environmental determinants. We first constructed a musculoskeletal protein pool by integrating transcriptomic enrichment, protein functional annotation, and literature expertise. Two musculoskeletal aging clocks\u2014MSKAge and MSKAgeMort\u2014were then developed using proteomic data of 21,070 UK Biobank participants. Acceleration metric (MSKAgeAccel\/MSKAgeMortAccel) quantified deviations of biological age from chronological age, with positive values indicating accelerated musculoskeletal aging. Associations of MSKAgeAccel\/MSKAgeMortAccel with mortality, musculoskeletal disorders, and age\u2010related diseases were assessed using Cox proportional hazards models. Environmental and genetic determinants were evaluated by linear regression and genome\u2010wide association analyses, respectively. Drug repurposing was used to identify potential targets of musculoskeletal diseases. A total of 39 musculoskeletal\u2010related proteins constituted the pool. Leveraging these proteins, MSKAge (\n                    <jats:italic>r<\/jats:italic>\n                    <jats:sub>female<\/jats:sub>\n                    \u2009=\u20090.62;\n                    <jats:italic>r<\/jats:italic>\n                    <jats:sub>male<\/jats:sub>\n                    \u2009=\u20090.56) and MSKAgeMort (\n                    <jats:italic>r<\/jats:italic>\n                    <jats:sub>female<\/jats:sub>\n                    \u2009=\u20090.93;\n                    <jats:italic>r<\/jats:italic>\n                    <jats:sub>male<\/jats:sub>\n                    \u2009=\u20090.88) were constructed. Both MSKAgeAccel and (in particular) MSKAgeMortAccel predicted mortality, musculoskeletal diseases, and age\u2010related diseases effectively. MSKAgeMortAccel showed significant associations with musculoskeletal disorders, including osteoarthritis, rheumatoid arthritis, gout, and low back pain. MSKAgeMortAccel was influenced by environmental pollutants, psychological factors, and unhealthy lifestyles. Genetic analyses revealed 13 variants and 71 genes enriched in epigenetic regulation and extracellular environment\u2010receptor interaction. Zinc was identified as a candidate musculoskeletal drug. We established a reliable musculoskeletal aging clock and elucidated genetic and environmental determinants. This framework enables stratification of individuals at risk of accelerated musculoskeletal aging, paving the way for anti\u2010aging interventions.\n                  <\/jats:p>","DOI":"10.1111\/acel.70636","type":"journal-article","created":{"date-parts":[[2026,7,26]],"date-time":"2026-07-26T03:57:51Z","timestamp":1785038271000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Construction and Validation of Plasma Protein\u2010Based Musculoskeletal Biological Age and Genetic and Environmental Risk Profiles"],"prefix":"10.1111","volume":"25","author":[{"given":"Yangdan","family":"Zhong","sequence":"first","affiliation":[{"name":"Department of Nutrition and Food Hygiene, West China School of Public Health and West China Fourth Hospital Sichuan University  Chengdu China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maoyao","family":"Xia","sequence":"additional","affiliation":[{"name":"Department of Nutrition and Food Hygiene, West China School of Public Health and West China Fourth Hospital Sichuan University  Chengdu China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6754-9773","authenticated-orcid":false,"given":"Xunying","family":"Zhao","sequence":"additional","affiliation":[{"name":"Department of Epidemiology and Health Statistics, West China School of Public Health and West China Fourth Hospital Sichuan University  Chengdu China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yang","family":"Qu","sequence":"additional","affiliation":[{"name":"Department of Epidemiology and Health Statistics, West China School of Public Health and West China Fourth Hospital Sichuan University  Chengdu China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bowen","family":"Lei","sequence":"additional","affiliation":[{"name":"Department of Epidemiology and Health Statistics, West China School of Public Health and West China Fourth Hospital Sichuan University  Chengdu China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sirui","family":"Zhen","sequence":"additional","affiliation":[{"name":"Department of Nutrition and Food Hygiene, West China School of Public Health and West China Fourth Hospital Sichuan University  Chengdu China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tao","family":"Han","sequence":"additional","affiliation":[{"name":"Department of Nutrition and Food Hygiene, West China School of Public Health and West China Fourth Hospital Sichuan University  Chengdu China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rong","family":"Xiang","sequence":"additional","affiliation":[{"name":"Department of Nutrition and Food Hygiene, West China School of Public Health and West China Fourth Hospital Sichuan University  Chengdu 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University  Chengdu China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zuyun","family":"Liu","sequence":"additional","affiliation":[{"name":"Second Affiliated Hospital, School of Public Health, Zhejiang Key Laboratory of Intelligent Preventive Medicine Zhejiang University School of Medicine  Hangzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xia","family":"Jiang","sequence":"additional","affiliation":[{"name":"Department of Nutrition and Food Hygiene, West China School of Public Health and West China Fourth Hospital Sichuan University  Chengdu China"},{"name":"Department of Epidemiology and Health Statistics, West China School of Public Health and West China Fourth Hospital Sichuan University  Chengdu China"},{"name":"Department of Clinical Neuroscience Karolinska Institutet  Stockholm 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