{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,26]],"date-time":"2026-08-26T11:01:28Z","timestamp":1787742088618,"version":"build-2784847793"},"reference-count":64,"publisher":"Oxford University Press (OUP)","issue":"3","license":[{"start":{"date-parts":[[2025,1,16]],"date-time":"2025-01-16T00:00:00Z","timestamp":1736985600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"DOI":"10.13039\/100009033","name":"NHSBT","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100009033","id-type":"DOI","asserted-by":"publisher"}]},{"name":"NIHR Blood and Transplant Research Unit in Donor Health and Genomics","award":["BTRU-2014-10024"],"award-info":[{"award-number":["BTRU-2014-10024"]}]},{"DOI":"10.13039\/501100000265","name":"UK Medical Research Council","doi-asserted-by":"publisher","award":["G0800270"],"award-info":[{"award-number":["G0800270"]}],"id":[{"id":"10.13039\/501100000265","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000274","name":"British Heart Foundation","doi-asserted-by":"publisher","award":["SP\/09\/002"],"award-info":[{"award-number":["SP\/09\/002"]}],"id":[{"id":"10.13039\/501100000274","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100018956","name":"NIHR Cambridge Biomedical Research Centre","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100018956","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Research and Development Programme of NHSBT"},{"name":"NHSBT Howard Ostin Trust Fund"},{"DOI":"10.13039\/501100013373","name":"NIHR Oxford Biomedical Research Centre","doi-asserted-by":"publisher","award":["NIHR-RP-PG-0310-1004"],"award-info":[{"award-number":["NIHR-RP-PG-0310-1004"]}],"id":[{"id":"10.13039\/501100013373","id-type":"DOI","asserted-by":"publisher"}]},{"name":"VENI","award":["916.14.023"],"award-info":[{"award-number":["916.14.023"]}]},{"DOI":"10.13039\/100007214","name":"VELUX Stiftung","doi-asserted-by":"crossref","award":["1156"],"award-info":[{"award-number":["1156"]}],"id":[{"id":"10.13039\/100007214","id-type":"DOI","asserted-by":"crossref"}]},{"name":"King Abdullah Scholarship Program and King Faisal Specialist Hospital & Research Center","award":["1012879283"],"award-info":[{"award-number":["1012879283"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2025,2,10]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Chronological age is a major risk factor for numerous diseases. However, chronological age does not capture the complex biological aging process. The difference between chronological age and biologically driven aging could be more informative in reflecting health status. Here, we set out to develop a metabolomic age prediction model by applying ridge regression and bootstrapping with 826 metabolites (678 endogenous and 148 xenobiotics) measured by an untargeted platform in relatively healthy blood donors aged 18\u201375 years from the INTERVAL study (N\u2005=\u200511\u2005977; 50.2% men). After bootstrapping internal validation, the metabolomic age prediction models demonstrated high performance with an adjusted R2 of 0.83 using all metabolites and 0.82 using only endogenous metabolites. The former was significantly associated with obesity and cardiovascular disease in the Netherlands Epidemiology of Obesity study (N\u2005=\u2005599; 47.0% men; age range\u2005=\u200545\u201365) due to the contribution of medication-derived metabolites\u2014namely salicylate and ibuprofen\u2014and environmental exposures such as cotinine. Additional metabolomic age prediction models using all metabolites were developed for men and women separately. The models had high performance (R\u00b2\u2005=\u20050.85 and 0.86) but shared a moderate correlation of 0.72. Furthermore, we observed 163 sex-dimorphic metabolites, including threonine, glycine, cholesterol, and androgenic and progesterone-related metabolites. Our strongest predictors across all models were novel and included hydroxyasparagine (Model Endo\u2005+\u2005Xeno \u03b2\u2005=\u20054.74), vanillylmandelate (\u03b2\u2005=\u20054.07), and 5,6-dihydrouridine (\u03b2\u2005=\u2005\u22124.2). Our study presents a robust metabolomic age model that reveals distinct sex-based age-related metabolic patterns and illustrates the value of including xenobiotic to enhance metabolomic prediction accuracy.<\/jats:p>","DOI":"10.1093\/gerona\/glae280","type":"journal-article","created":{"date-parts":[[2025,1,14]],"date-time":"2025-01-14T07:15:30Z","timestamp":1736838930000},"source":"Crossref","is-referenced-by-count":13,"title":["Robust Metabolomic Age Prediction Based on a Wide Selection of Metabolites"],"prefix":"10.1093","volume":"80","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8026-2251","authenticated-orcid":false,"given":"Tariq O","family":"Faquih","sequence":"first","affiliation":[{"name":"Department of Clinical Epidemiology, Leiden University Medical Center , Leiden ,","place":["The Netherlands"]},{"name":"Division of Sleep and Circadian Disorders, Brigham and Women\u2019s Hospital , Boston, Massachusetts ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Astrid","family":"van Hylckama Vlieg","sequence":"additional","affiliation":[{"name":"Department of Clinical Epidemiology, Leiden University Medical Center , Leiden ,","place":["The Netherlands"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Praveen","family":"Surendran","sequence":"additional","affiliation":[{"name":"Division of Sleep and Circadian Disorders, Brigham and Women\u2019s Hospital , Boston, Massachusetts ,","place":["USA"]},{"name":"GSK plc., Stevenage , England ,","place":["UK"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Adam S","family":"Butterworth","sequence":"additional","affiliation":[{"name":"Division of Sleep and Circadian Disorders, Brigham and Women\u2019s Hospital , Boston, Massachusetts ,","place":["USA"]},{"name":"British Heart Foundation Cardiovascular Epidemiology Unit, Department of Public Health and Primary Care, University of Cambridge , Cambridge ,","place":["UK"]},{"name":"NIHR Blood and Transplant Research Unit in Donor Health and Behaviour, Department of Public Health and Primary Care, University of Cambridge , Cambridge ,","place":["UK"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ruifang","family":"Li-Gao","sequence":"additional","affiliation":[{"name":"Department of Clinical Epidemiology, Leiden University Medical Center , Leiden ,","place":["The Netherlands"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ren\u00e9e","family":"de Mutsert","sequence":"additional","affiliation":[{"name":"Department of Clinical Epidemiology, Leiden University Medical Center , Leiden ,","place":["The Netherlands"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2558-7496","authenticated-orcid":false,"given":"Frits R","family":"Rosendaal","sequence":"additional","affiliation":[{"name":"Department of Clinical Epidemiology, Leiden University Medical Center , Leiden ,","place":["The Netherlands"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7801-809X","authenticated-orcid":false,"given":"Raymond","family":"Noordam","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Section of Gerontology and Geriatrics, Leiden University Medical Center , Leiden ,","place":["The Netherlands"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8526-7748","authenticated-orcid":false,"given":"Diana","family":"van Heemst","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Section of Gerontology and Geriatrics, Leiden University Medical Center , Leiden ,","place":["The Netherlands"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ko","family":"Willems van Dijk","sequence":"additional","affiliation":[{"name":"Department of Human Genetics, Leiden University Medical Center , Leiden ,","place":["The Netherlands"]},{"name":"Einthoven Laboratory for Experimental Vascular Medicine, Leiden University Medical Center , Leiden ,","place":["The Netherlands"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dennis O","family":"Mook-Kanamori","sequence":"additional","affiliation":[{"name":"Department of Clinical Epidemiology, Leiden University Medical Center , Leiden ,","place":["The Netherlands"]},{"name":"Department of Public Health and Primary Care, Leiden University Medical Center , Leiden ,","place":["The Netherlands"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2025,1,16]]},"reference":[{"issue":"8","key":"2025073104264122500_CIT0001","doi-asserted-by":"publisher","first-page":"1097","DOI":"10.1161\/CIRCRESAHA.111.246876","article-title":"The intersection between aging and cardiovascular disease","volume":"110","author":"North","year":"2012","journal-title":"Circ 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