{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,17]],"date-time":"2026-08-17T14:47:26Z","timestamp":1786978046439,"version":"build-2736575974"},"reference-count":54,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2024,11,25]],"date-time":"2024-11-25T00:00:00Z","timestamp":1732492800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2024,11,25]],"date-time":"2024-11-25T00:00:00Z","timestamp":1732492800000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82273709"],"award-info":[{"award-number":["82273709"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["J cachexia sarcopenia muscle"],"published-print":{"date-parts":[[2025,2]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Bilirubin is a by\u2010product of haemoglobin breakdown and has been reported to be a potent antioxidant recently. While elevated levels of bilirubin have been linked to a reduced risk of various diseases, their role remains unknown in frailty. This study aims to explore the relationship between serum bilirubin levels and the risk of frailty.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>This cohort study included 442\u2009223 White British participants (aged 39 to 73\u2009years) with an available frailty index at baseline (2006 to 2010) from the UK Biobank. The associations of total\/direct bilirubin levels with the continuous frailty index were analysed by multivariable linear regression, and multivariable logistic regression was used after classifying frailty outcomes into non\u2010frailty, pre\u2010frailty and frailty. A Mendelian randomization (MR) analysis was applied to evaluate the association of genetically predicted bilirubin levels with frailty risk.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      The prevalence rates of both pre\u2010frailty and frailty were 46.17% and 12.49%, respectively, with higher rates observed in women than in men (pre\u2010frailty: 47.33% vs. 44.79%, frailty: 13.64% vs. 11.13%, respectively). There was a non\u2010linear negative association between total bilirubin levels and frailty indexes (\n                      <jats:italic>p<\/jats:italic>\n                      \u2009&lt;\u20090.0001). Mildly elevated total bilirubin levels had protective effects against pre\u2010frailty (OR\u2009=\u20090.863, 95% CI: 0.849 to 0.879,\n                      <jats:italic>p<\/jats:italic>\n                      \u2009&lt;\u20090.001) and frailty (OR\u2009=\u20090.660, 95% CI: 0.641 to 0.679,\n                      <jats:italic>p<\/jats:italic>\n                      \u2009&lt;\u20090.001). Increased total bilirubin levels were more beneficial for women with frailty risk (percent changes per SD \u03bcmol\/L\u2009=\u2009\u22120.37%, 95% CI: \u22120.40% to \u22120.34%). The MR analysis revealed a negative association between genetically predicted total\/direct bilirubin levels and frailty risk (both\n                      <jats:italic>p<\/jats:italic>\n                      \u2009&lt;\u20090.0001).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Circulating total\/direct bilirubin levels were negatively associated with frailty risk in White British individuals. Mildly elevated total bilirubin levels were more beneficial for women subpopulation.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/jcsm.13642","type":"journal-article","created":{"date-parts":[[2024,11,25]],"date-time":"2024-11-25T04:04:31Z","timestamp":1732507471000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Assessing Association Between Circulating Bilirubin Levels and the Risk of Frailty: An Observational and Mendelian Randomization Study"],"prefix":"10.1002","volume":"16","author":[{"given":"Jun","family":"Wu","sequence":"first","affiliation":[{"name":"Department of Epidemiology and Biostastics, School of Public Health, Shunde Women and Children's Hospital Guangdong Medical University  Dongguan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jia\u2010hao","family":"Xu","sequence":"additional","affiliation":[{"name":"Department of Epidemiology and Biostastics, School of Public Health, Shunde Women and Children's Hospital Guangdong Medical University  Dongguan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hao\u2010qi","family":"Zou","sequence":"additional","affiliation":[{"name":"Department of Epidemiology and Biostastics, School of Public Health, Shunde Women and Children's Hospital Guangdong Medical University  Dongguan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yi\u2010jiang","family":"Ouyang","sequence":"additional","affiliation":[{"name":"Department of Epidemiology and Biostastics, School of Public Health, Shunde Women and Children's Hospital Guangdong Medical University  Dongguan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shang\u2010jie","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Epidemiology and Biostastics, School of Public Health, Shunde Women and Children's Hospital Guangdong Medical University  Dongguan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Liang","family":"Wu","sequence":"additional","affiliation":[{"name":"Department of Epidemiology and Biostastics, School of Public Health, Shunde Women and Children's Hospital Guangdong Medical University  Dongguan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jie","family":"Zhang","sequence":"additional","affiliation":[{"name":"School of Public Health Anhui University of Science and Technology  Hefei Anhui China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ming\u2010Juan","family":"Yin","sequence":"additional","affiliation":[{"name":"Department of Epidemiology and Biostastics, School of Public Health, Shunde Women and Children's Hospital Guangdong Medical University  Dongguan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dong\u2010qing","family":"Ye","sequence":"additional","affiliation":[{"name":"School of Public Health Anhui University of Science and Technology  Hefei Anhui China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5413-8353","authenticated-orcid":false,"given":"Jin\u2010dong","family":"Ni","sequence":"additional","affiliation":[{"name":"Department of Epidemiology and Biostastics, School of Public Health, Shunde Women and Children's Hospital Guangdong Medical University  Dongguan China"},{"name":"Precision Key Laboratory of Public Health Guangdong Medical University  Dongguan 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L.","year":"2009","journal-title":"Bioscience Trends"},{"key":"e_1_2_10_51_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMcibr2013250"},{"key":"e_1_2_10_52_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.RA120.013700"},{"key":"e_1_2_10_53_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajpendo.00405.2020"},{"key":"e_1_2_10_54_1","doi-asserted-by":"publisher","DOI":"10.3389\/fphar.2020.594574"},{"key":"e_1_2_10_55_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pgen.1010823"}],"container-title":["Journal of Cachexia, Sarcopenia and Muscle"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/jcsm.13642","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/jcsm.13642","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/jcsm.13642","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,4,12]],"date-time":"2026-04-12T07:30:25Z","timestamp":1775979025000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/jcsm.13642"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,11,25]]},"references-count":54,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2025,2]]}},"alternative-id":["10.1002\/jcsm.13642"],"URL":"https:\/\/doi.org\/10.1002\/jcsm.13642","archive":["Portico"],"relation":{},"ISSN":["2190-5991","2190-6009"],"issn-type":[{"value":"2190-5991","type":"print"},{"value":"2190-6009","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,11,25]]},"assertion":[{"value":"2023-11-20","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2024-10-17","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2024-11-25","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e13642"}}