{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,4]],"date-time":"2026-11-04T17:41:35Z","timestamp":1793814095946,"version":"4.6.1"},"reference-count":40,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2026,7,4]],"date-time":"2026-07-04T00:00:00Z","timestamp":1783123200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0"},{"start":{"date-parts":[[2026,10,28]],"date-time":"2026-10-28T00:00:00Z","timestamp":1793145600000},"content-version":"vor","delay-in-days":116,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0"}],"funder":[{"name":"National Institute on Aging, United States","award":["R03AG095722"],"award-info":[{"award-number":["R03AG095722"]}],"id":[{"id":"https:\/\/ror.org\/049v75w11","id-type":"ROR","asserted-by":"crossref"}]},{"name":"Foundation for Anesthesia Education and Research, United States","id":[{"id":"https:\/\/ror.org\/04d16a047","id-type":"ROR","asserted-by":"crossref"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["npj Aging"],"DOI":"10.1038\/s41514-026-00441-2","type":"journal-article","created":{"date-parts":[[2026,7,4]],"date-time":"2026-07-04T16:14:28Z","timestamp":1783181668000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Biological aging increases risk of postoperative morbidity and mortality: an international, multi-cohort study"],"prefix":"10.1038","volume":"12","author":[{"given":"Joseph R.","family":"Scarpa","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M. Cary","family":"Reid","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Olivier","family":"Elemento","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jan","family":"Krumsiek","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,7,4]]},"reference":[{"key":"441_CR1","doi-asserted-by":"publisher","first-page":"87","DOI":"10.1097\/SLA.0000000000005077","volume":"277","author":"RD Becher","year":"2023","unstructured":"Becher, R. D., Vander Wyk, B., Leo-Summers, L., Desai, M. M. & Gill, T. M. The incidence and cumulative risk of major surgery in older persons in the United States. Ann. Surg. 277, 87\u201392 (2023).","journal-title":"Ann. Surg."},{"key":"441_CR2","doi-asserted-by":"publisher","first-page":"549","DOI":"10.1016\/S0140-6736(14)61347-7","volume":"385","author":"MJ Prince","year":"2015","unstructured":"Prince, M. J. et al. The burden of disease in older people and implications for health policy and practice. Lancet 385, 549\u2013562 (2015).","journal-title":"Lancet"},{"key":"441_CR3","doi-asserted-by":"publisher","first-page":"e225155","DOI":"10.1001\/jamasurg.2022.5155","volume":"157","author":"TM Gill","year":"2022","unstructured":"Gill, T. M., Vander Wyk, B., Leo-Summers, L., Murphy, T. E. & Becher, R. D. Population-based estimates of 1-year mortality after major surgery among community-living older US adults. JAMA Surg. 157, e225155 (2022).","journal-title":"JAMA Surg."},{"key":"441_CR4","doi-asserted-by":"publisher","first-page":"762","DOI":"10.1016\/j.jamcollsurg.2004.05.280","volume":"199","author":"VA Lawrence","year":"2004","unstructured":"Lawrence, V. A. et al. Functional independence after major abdominal surgery in the elderly. J. Am. Coll. Surg. 199, 762\u2013772 (2004).","journal-title":"J. Am. Coll. Surg."},{"key":"441_CR5","doi-asserted-by":"publisher","first-page":"37","DOI":"10.1016\/j.jamcollsurg.2011.01.056","volume":"213","author":"TN Robinson","year":"2011","unstructured":"Robinson, T. N. et al. Accumulated frailty characteristics predict postoperative discharge institutionalization in the geriatric patient. J. Am. Coll. Surg. 213, 37\u201342 (2011).","journal-title":"J. Am. Coll. Surg."},{"key":"441_CR6","doi-asserted-by":"publisher","first-page":"E4104","DOI":"10.1073\/pnas.1506264112","volume":"112","author":"DW Belsky","year":"2015","unstructured":"Belsky, D. W. et al. Quantification of biological aging in young adults. Proc. Natl. Acad. Sci. USA. 112, E4104\u2013E4110 (2015).","journal-title":"Proc. Natl. Acad. Sci. USA."},{"key":"441_CR7","doi-asserted-by":"publisher","first-page":"573","DOI":"10.18632\/aging.101414","volume":"10","author":"ME Levine","year":"2018","unstructured":"Levine, M. E. et al. An epigenetic biomarker of aging for lifespan and healthspan. Aging 10, 573\u2013591 (2018).","journal-title":"Aging"},{"key":"441_CR8","doi-asserted-by":"publisher","first-page":"e1002718","DOI":"10.1371\/journal.pmed.1002718","volume":"15","author":"Z Liu","year":"2018","unstructured":"Liu, Z. et al. A new aging measure captures morbidity and mortality risk across diverse subpopulations from NHANES IV: a cohort study. PLoS Med. 15, e1002718 (2018).","journal-title":"PLoS Med."},{"key":"441_CR9","doi-asserted-by":"publisher","first-page":"1132","DOI":"10.1038\/s43587-025-00866-6","volume":"5","author":"A Balachandran","year":"2025","unstructured":"Balachandran, A. et al. Pace of aging analysis of healthspan and lifespan in older adults in the US and UK. Nat. Aging 5, 1132\u20131142 (2025).","journal-title":"Nat. Aging"},{"key":"441_CR10","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-025-57032-0","volume":"16","author":"M Arnold","year":"2025","unstructured":"Arnold, M. et al. Individual bioenergetic capacity as a potential source of resilience to Alzheimer\u2019s disease. Nat. Commun. 16, 1910 (2025).","journal-title":"Nat. Commun."},{"key":"441_CR11","doi-asserted-by":"publisher","first-page":"249","DOI":"10.1016\/j.hrtlng.2023.08.010","volume":"62","author":"KM Ho","year":"2023","unstructured":"Ho, K. M. Biological age as a predictor of unplanned intensive care readmission during the same hospitalization. Heart Lung 62, 249\u2013255 (2023).","journal-title":"Heart Lung"},{"key":"441_CR12","doi-asserted-by":"publisher","DOI":"10.1002\/jcsm.70046","volume":"16","author":"JL Sanchez-Sanchez","year":"2025","unstructured":"Sanchez-Sanchez, J. L. et al. Biological ageing acceleration and functional capacities across the lifespan in the inspIRE-T cohort. J. Cachexia Sarcopenia Muscle 16, e70046 (2025).","journal-title":"J. Cachexia Sarcopenia Muscle"},{"key":"441_CR13","doi-asserted-by":"publisher","first-page":"e2223285","DOI":"10.1001\/jamanetworkopen.2022.23285","volume":"5","author":"P Jain","year":"2022","unstructured":"Jain, P. et al. Analysis of epigenetic age acceleration and healthy longevity among older US women. JAMA Netw. Open 5, e2223285 (2022).","journal-title":"JAMA Netw. Open"},{"key":"441_CR14","doi-asserted-by":"publisher","DOI":"10.1038\/s41597-024-03517-4","volume":"11","author":"L Lim","year":"2024","unstructured":"Lim, L. et al. INSPIRE, a publicly available research dataset for perioperative medicine. Sci. Data 11, 655 (2024).","journal-title":"Sci. Data"},{"key":"441_CR15","doi-asserted-by":"publisher","DOI":"10.1093\/jamiaopen\/ooad084","volume":"6","author":"M Samad","year":"2023","unstructured":"Samad, M. et al. Medical informatics operating room vitals and events repository (MOVER): a public-access operating room database. JAMIA Open 6, ooad084 (2023).","journal-title":"JAMIA Open"},{"key":"441_CR16","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-025-12495-5","volume":"15","author":"KJS Kwan","year":"2025","unstructured":"Kwan, K. J. S. et al. Evaluating the potential of phenotypic age to enhance cardiovascular risk prediction over chronological age in the UK Biobank. Sci. Rep. 15, 27858 (2025).","journal-title":"Sci. Rep."},{"key":"441_CR17","doi-asserted-by":"publisher","DOI":"10.1161\/JAHA.123.032847","volume":"13","author":"SN Forrester","year":"2024","unstructured":"Forrester, S. N., Baek, J., Hou, L., Roger, V. & Kiefe, C. I. A comparison of 5 measures of accelerated biological aging and their association with incident cardiovascular disease: the CARDIA study. J. Am. Heart Assoc. 13, e032847 (2024).","journal-title":"J. Am. Heart Assoc."},{"key":"441_CR18","doi-asserted-by":"publisher","first-page":"2795","DOI":"10.1007\/s11357-021-00480-5","volume":"43","author":"D Kwon","year":"2021","unstructured":"Kwon, D. & Belsky, D. W. A toolkit for quantification of biological age from blood chemistry and organ function test data: BioAge. Geroscience 43, 2795\u20132808 (2021).","journal-title":"Geroscience"},{"key":"441_CR19","doi-asserted-by":"publisher","first-page":"240","DOI":"10.1016\/j.mad.2005.10.004","volume":"127","author":"P Klemera","year":"2006","unstructured":"Klemera, P. & Doubal, S. A new approach to the concept and computation of biological age. Mech. Ageing Dev. 127, 240\u2013248 (2006).","journal-title":"Mech. Ageing Dev."},{"key":"441_CR20","doi-asserted-by":"publisher","DOI":"10.1002\/advs.202501765","volume":"12","author":"M Hao","year":"2025","unstructured":"Hao, M. et al. Gompertz law-based biological age (GOLD BioAge): a simple and practical measurement of biological ageing to capture morbidity and mortality risks. Adv. Sci. 12, e01765 (2025).","journal-title":"Adv. Sci."},{"key":"441_CR21","doi-asserted-by":"publisher","DOI":"10.1126\/sciadv.adp3743","volume":"10","author":"J Mutz","year":"2024","unstructured":"Mutz, J., Iniesta, R. & Lewis, C. M. Metabolomic age (MileAge) predicts health and life span: a comparison of multiple machine learning algorithms. Sci. Adv. 10, eadp3743 (2024).","journal-title":"Sci. Adv."},{"key":"441_CR22","doi-asserted-by":"publisher","first-page":"2450","DOI":"10.1038\/s41591-024-03164-7","volume":"30","author":"MA Argentieri","year":"2024","unstructured":"Argentieri, M. A. et al. Proteomic aging clock predicts mortality and risk of common age-related diseases in diverse populations. Nat. Med. 30, 2450\u20132460 (2024).","journal-title":"Nat. Med."},{"key":"441_CR23","doi-asserted-by":"publisher","first-page":"e117","DOI":"10.1093\/gerona\/glab078","volume":"76","author":"A Marquez-Salinas","year":"2021","unstructured":"Marquez-Salinas, A. et al. Adaptive metabolic and inflammatory responses identified using accelerated aging metrics are linked to adverse outcomes in severe SARS-CoV-2 infection. J. Gerontol. A Biol. Sci. Med Sci. 76, e117\u2013e126 (2021).","journal-title":"J. Gerontol. A Biol. Sci. Med Sci."},{"key":"441_CR24","doi-asserted-by":"publisher","first-page":"255ra131","DOI":"10.1126\/scitranslmed.3009701","volume":"6","author":"B Gaudilliere","year":"2014","unstructured":"Gaudilliere, B. et al. Clinical recovery from surgery correlates with single-cell immune signatures. Sci. Transl. Med. 6, 255ra131 (2014).","journal-title":"Sci. Transl. Med."},{"key":"441_CR25","doi-asserted-by":"publisher","DOI":"10.1016\/j.isci.2020.101659","volume":"23","author":"A Tsurumi","year":"2020","unstructured":"Tsurumi, A. et al. Multi-Biomarker Prediction Models for Multiple Infection Episodes Following Blunt Trauma. iScience 23, 101659 (2020).","journal-title":"iScience"},{"key":"441_CR26","doi-asserted-by":"publisher","first-page":"582","DOI":"10.1097\/SLA.0000000000005348","volume":"275","author":"KK Rumer","year":"2022","unstructured":"Rumer, K. K. et al. Integrated single-cell and plasma proteomic modeling to predict surgical site complications: a prospective cohort study. Ann. Surg. 275, 582\u2013590 (2022).","journal-title":"Ann. Surg."},{"key":"441_CR27","doi-asserted-by":"publisher","first-page":"6358","DOI":"10.1016\/j.cell.2024.08.021","volume":"187","author":"Y Yang","year":"2024","unstructured":"Yang, Y. et al. Metformin decelerates aging clock in male monkeys. Cell 187, 6358\u201378 e29 (2024).","journal-title":"Cell"},{"key":"441_CR28","doi-asserted-by":"publisher","first-page":"997","DOI":"10.1038\/s43587-025-00841-1","volume":"5","author":"S Liesenfelder","year":"2025","unstructured":"Liesenfelder, S. et al. Epigenetic editing at individual age-associated CpGs affects the genome-wide epigenetic aging landscape. Nat. Aging 5, 997\u20131009 (2025).","journal-title":"Nat. Aging"},{"key":"441_CR29","doi-asserted-by":"publisher","first-page":"1026","DOI":"10.1093\/aje\/kwx246","volume":"186","author":"A Fry","year":"2017","unstructured":"Fry, A. et al. Comparison of sociodemographic and health-related characteristics of uk biobank participants with those of the general population. Am. J. Epidemiol. 186, 1026\u20131034 (2017).","journal-title":"Am. J. Epidemiol."},{"key":"441_CR30","doi-asserted-by":"publisher","first-page":"174","DOI":"10.1093\/bja\/aex223","volume":"119","author":"S Venkatesan","year":"2017","unstructured":"Venkatesan, S. et al. Cohort study of preoperative blood pressure and risk of 30-day mortality after elective non-cardiac surgery. Br. J. Anaesth. 119, 174 (2017).","journal-title":"Br. J. Anaesth."},{"key":"441_CR31","doi-asserted-by":"publisher","first-page":"439","DOI":"10.1001\/jamasurg.2014.4","volume":"149","author":"LG Glance","year":"2014","unstructured":"Glance, L. G. et al. Hospital readmission after noncardiac surgery: the role of major complications. JAMA Surg. 149, 439\u2013445 (2014).","journal-title":"JAMA Surg."},{"key":"441_CR32","doi-asserted-by":"publisher","DOI":"10.1016\/j.atherosclerosis.2023.117437","volume":"389","author":"P Welsh","year":"2024","unstructured":"Welsh, P. et al. Elevated lipoprotein(a) increases risk of subsequent major adverse cardiovascular events (MACE) and coronary revascularisation in incident ASCVD patients: a cohort study from the UK Biobank. Atherosclerosis 389, 117437 (2024).","journal-title":"Atherosclerosis"},{"key":"441_CR33","doi-asserted-by":"publisher","first-page":"838","DOI":"10.1097\/SLA.0000000000002839","volume":"268","author":"R de la Plaza Llamas","year":"2018","unstructured":"de la Plaza Llamas, R. et al. Clinical validation of the comprehensive complication index as a measure of postoperative morbidity at a surgical department: a prospective study. Ann. Surg. 268, 838\u2013844 (2018).","journal-title":"Ann. Surg."},{"key":"441_CR34","doi-asserted-by":"publisher","first-page":"676","DOI":"10.1093\/aje\/kwq433","volume":"173","author":"H Quan","year":"2011","unstructured":"Quan, H. et al. Updating and validating the Charlson comorbidity index and score for risk adjustment in hospital discharge abstracts using data from 6 countries. Am. J. Epidemiol. 173, 676\u2013682 (2011).","journal-title":"Am. J. Epidemiol."},{"key":"441_CR35","doi-asserted-by":"publisher","first-page":"2941","DOI":"10.1007\/s00586-020-06595-1","volume":"29","author":"AF Mannion","year":"2020","unstructured":"Mannion, A. F. et al. Can the Charlson Comorbidity Index be used to predict the ASA grade in patients undergoing spine surgery? Eur. Spine J. 29, 2941\u20132952 (2020).","journal-title":"Eur. Spine J."},{"key":"441_CR36","doi-asserted-by":"publisher","first-page":"e350","DOI":"10.1016\/S2589-7500(23)00043-2","volume":"5","author":"R Jiang","year":"2023","unstructured":"Jiang, R. et al. Associations of physical frailty with health outcomes and brain structure in 483 033 middle-aged and older adults: a population-based study from the UK Biobank. Lancet Digit. Health 5, e350\u2013e359 (2023).","journal-title":"Lancet Digit. Health"},{"key":"441_CR37","doi-asserted-by":"publisher","first-page":"l4466","DOI":"10.1136\/bmj.l4466","volume":"366","author":"BM Krause","year":"2019","unstructured":"Krause, B. M., Sabia, S., Manning, H. J., Singh-Manoux, A. & Sanders, R. D. Association between major surgical admissions and the cognitive trajectory: 19 year follow-up of Whitehall II cohort study. BMJ 366, l4466 (2019).","journal-title":"BMJ"},{"key":"441_CR38","doi-asserted-by":"publisher","first-page":"764","DOI":"10.1002\/bimj.201800240","volume":"62","author":"RM Pfeiffer","year":"2020","unstructured":"Pfeiffer, R. M. & Gail, M. H. Estimating the decision curve and its precision from three study designs. Biom. J. 62, 764\u2013776 (2020).","journal-title":"Biom. J."},{"key":"441_CR39","unstructured":"Lundberg S. M., Lee S. I. A Unified Approach to Interpreting Model Predictions. Adv Neural Inform. syst. 30, 4768\u20134777 (2017)."},{"key":"441_CR40","doi-asserted-by":"publisher","first-page":"e294","DOI":"10.1097\/SLA.0000000000005027","volume":"277","author":"Q Yan","year":"2023","unstructured":"Yan, Q. et al. Association of frailty and the expanded operative stress score with preoperative acute serious conditions, complications, and mortality in males compared to females: a retrospective observational study. Ann. Surg. 277, e294\u2013e304 (2023).","journal-title":"Ann. Surg."}],"container-title":["npj Aging"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.nature.com\/articles\/s41514-026-00441-2","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41514-026-00441-2.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41514-026-00441-2.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,10,27]],"date-time":"2026-10-27T23:23:55Z","timestamp":1793143435000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/s41514-026-00441-2"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,7,4]]},"references-count":40,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2026,12]]}},"alternative-id":["441"],"URL":"https:\/\/doi.org\/10.1038\/s41514-026-00441-2","relation":{},"ISSN":["2731-6068"],"issn-type":[{"value":"2731-6068","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,7,4]]},"assertion":[{"value":"25 March 2026","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"26 June 2026","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"4 July 2026","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"O.E. is supported by Janssen, J&J, Astrazeneca, Volastra, and Eli Lilly research grants. He is a scientific advisor and equity holder in Freenome, Owkin, Volastra Therapeutics, and One Three Biotech and a paid scientific advisor to Champions Oncology and Pionyr Immunotherapeutics. JK is a confounder of iollo, advisor to Everfur, and advisor\/part-time employee at ExactRx. JRS is an advisor at ExactRx. The other authors declare that they have no competing interests.","order":1,"name":"Ethics","label":"Competing interests","group":{"name":"EthicsHeading","label":"Ethics"}}],"article-number":"148"}}