{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,9]],"date-time":"2026-09-09T05:09:22Z","timestamp":1788930562386,"version":"build-2803163510"},"reference-count":33,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,9,9]],"date-time":"2026-09-09T00:00:00Z","timestamp":1788912000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>The complement system plays an important role in innate immunity and age-related inflammation, but its prognostic value in centenarians remains unclear. This study aimed to examine the associations between serum complement C3 and C4 levels and all-cause mortality among centenarians.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>We studied centenarians in Hainan Island, China. We used multivariable-adjusted restricted cubic splines, Cox proportional hazards models, and Kaplan\u2013Meier survival analysis to assess the relationships between serum C3 and C4 levels and all-cause mortality.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      A total of 906 centenarians were included in the final analysis. During a median follow-up of 30.1 months, 838 (92.5%) participants died. There was a significant inverse linear relationship between serum C3 levels and all-cause mortality (\n                      <jats:italic>P<\/jats:italic>\n                      = 0.031). Compared with the highest C3 quartile (Q4), individuals in the lowest quartile (Q1) had an increased risk of all-cause mortality (hazard ratio = 1.337; 95% confidence interval: 1.092\u20131.635;\n                      <jats:italic>P<\/jats:italic>\n                      = 0.005), whereas C4 levels showed no significant relationship with mortality (\n                      <jats:italic>P<\/jats:italic>\n                      &amp;gt; 0.05). When we used Q1 (0.86 g\/L) as a cut-off, centenarians with C3 levels below this threshold also showed a higher mortality risk than those above this threshold (hazard ratio = 1.250; 95% confidence interval: 1.063\u20131.470;\n                      <jats:italic>P<\/jats:italic>\n                      = 0.007). A Kaplan\u2013Meier analysis further indicated a shorter survival time in the lowest C3 quartile (Q1 vs. Q4: 26 vs. 34 months,\n                      <jats:italic>P<\/jats:italic>\n                      = 0.002). In contrast, C4 levels were not significantly associated with survival.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Serum complement C3 levels, but not C4 levels, might be associated with the risk of all-cause mortality in centenarians. However, because all centenarians were recruited from Hainan Island, external validation in other regions and ethnic populations is warranted.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fimmu.2026.1911948","type":"journal-article","created":{"date-parts":[[2026,9,9]],"date-time":"2026-09-09T04:41:59Z","timestamp":1788928919000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Low serum complement C3 levels are associated with all-cause mortality in Chinese centenarians: a prospective cohort study"],"prefix":"10.3389","volume":"17","author":[{"given":"WeiGuang","family":"Zhang","sequence":"first","affiliation":[{"name":"Department of Nephrology, Hainan Hospital of Chinese PLA General Hospital, Hainan Province Flexible Talent Attraction Collaborative Innovation Center","place":["Sanya, China"]},{"name":"Senior Department of Nephrology, Chinese PLA General Hospital, State Key Laboratory of Kidney Diseases, National Clinical Research Center for Kidney Diseases, Beijing Key Laboratory of Medical Devices and Integrated Traditional Chinese and Western Drug Development for Severe Kidney Diseases, Beijing Key Laboratory of Digital Intelligent TCM for the Prevention and Treatment of Pan-vascular Diseases, Key Disciplines of National Administration of Traditional Chinese Medicine (ZYYZDXK-2023310), Innovation Team and Talents Cultivation Program of National Administration of Traditional Chinese Medicine (ZYYCXTD-D-202402)","place":["Beijing, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuting","family":"Duan","sequence":"additional","affiliation":[{"name":"Department of Geriatric Medicine, The Affiliated Hospital of Qingdao University","place":["Qingdao, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhe","family":"Li","sequence":"additional","affiliation":[{"name":"Luoyang Key Laboratory of Clinical Multiomics and Translational Medicine, Henan Key Laboratory of Rare Diseases, Endocrinology and Metabolism Center, The First Affiliated Hospital, and College of Clinical Medicine of Henan University of Science and Technology","place":["Luoyang, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Miaomiao","family":"Liu","sequence":"additional","affiliation":[{"name":"Luoyang Key Laboratory of Clinical Multiomics and Translational Medicine, Henan Key Laboratory of Rare Diseases, Endocrinology and Metabolism Center, The First Affiliated Hospital, and College of Clinical Medicine of Henan University of Science and Technology","place":["Luoyang, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qiushi","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Nephrology, Hainan Hospital of Chinese PLA General Hospital, Hainan Province Flexible Talent Attraction Collaborative Innovation Center","place":["Sanya, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yang","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Laboratory Medicine, Hainan Hospital of Chinese PLA General Hospital","place":["Sanya, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zehao","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Nephrology, Hainan Hospital of Chinese PLA General Hospital, Hainan Province Flexible Talent Attraction Collaborative Innovation Center","place":["Sanya, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zeyu","family":"Qu","sequence":"additional","affiliation":[{"name":"Department of Nephrology, Hainan Hospital of Chinese PLA General Hospital, Hainan Province Flexible Talent Attraction Collaborative Innovation Center","place":["Sanya, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qiao","family":"Zhu","sequence":"additional","affiliation":[{"name":"Central Laboratory, Hainan Hospital of Chinese PLA General Hospital","place":["Sanya, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yali","family":"Zhao","sequence":"additional","affiliation":[{"name":"Central Laboratory, Hainan Hospital of Chinese PLA General Hospital","place":["Sanya, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Miao","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Anti-Nuclear, Biological, Chemical Medicine, the Graduate School of Chinese PLA General Hospital","place":["Beijing, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yao","family":"He","sequence":"additional","affiliation":[{"name":"Institute of Geriatrics, the Second Medical Center of Chinese PLA General Hospital, Beijing Key Laboratory of Geriatric Comorbidity, National Clinical Research Center for Geriatrics Diseases","place":["Beijing, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qing","family":"Luo","sequence":"additional","affiliation":[{"name":"Department of Nephrology, Hainan Hospital of Chinese PLA General Hospital, Hainan Province Flexible Talent Attraction Collaborative Innovation Center","place":["Sanya, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jie","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Nephrology, Hainan Hospital of Chinese PLA General Hospital, Hainan Province Flexible Talent Attraction Collaborative Innovation Center","place":["Sanya, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yizhi","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Nephrology, Hainan Hospital of Chinese PLA General Hospital, Hainan Province Flexible Talent Attraction Collaborative Innovation Center","place":["Sanya, China"]},{"name":"Senior Department of Nephrology, Chinese PLA General Hospital, State Key Laboratory of Kidney Diseases, National Clinical Research Center for Kidney Diseases, Beijing Key Laboratory of Medical Devices and Integrated Traditional Chinese and Western Drug Development for Severe Kidney Diseases, Beijing Key Laboratory of Digital Intelligent TCM for the Prevention and Treatment of Pan-vascular Diseases, Key Disciplines of National Administration of Traditional Chinese Medicine (ZYYZDXK-2023310), Innovation Team and Talents Cultivation Program of National Administration of Traditional Chinese Medicine (ZYYCXTD-D-202402)","place":["Beijing, China"]},{"name":"The Second School of Clinical Medicine, Southern Medical University","place":["Guangzhou, China"]},{"name":"Hainan Medical University","place":["Haikou, China"]},{"name":"Sanya Nephrology Medical Quality Control Center","place":["Sanya, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,9,9]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2025.03.011","article-title":"From geroscience to precision geromedicine: Understanding and managing aging","volume":"188","author":"Kroemer","year":"2025","journal-title":"Cell"},{"key":"B2","doi-asserted-by":"publisher","first-page":"652","DOI":"10.1016\/s0140-6736(99)01987-x","article-title":"Centenarians: the older you get, the healthier you have been","volume":"354","author":"Hitt","year":"1999","journal-title":"Lancet"},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.1016\/j.archger.2023.105175","article-title":"The biological age model for evaluating the degree of aging in centenarians","volume":"117","author":"Zhang","year":"2024","journal-title":"Arch Gerontol Geriatr"},{"key":"B4","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2012.03.047","article-title":"Complement C1q activates canonical Wnt signaling and promotes aging-related phenotypes","volume":"149","author":"Naito","year":"2012","journal-title":"Cell"},{"key":"B5","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.89.21.10016","article-title":"Complement activation by beta-amyloid in Alzheimer disease","volume":"89","author":"Rogers","year":"1992","journal-title":"Proc Natl Acad Sci USA"},{"key":"B6","doi-asserted-by":"publisher","DOI":"10.1016\/s0002-9440(10)64051-5","article-title":"Generation of C-reactive protein and complement components in atherosclerotic plaques","volume":"158","author":"Yasojima","year":"2001","journal-title":"Am J Pathol"},{"key":"B7","doi-asserted-by":"publisher","DOI":"10.1007\/s00018-021-03796-9","article-title":"The complement system in age-related macular degeneration","volume":"78","author":"Armento","year":"2021","journal-title":"Cell Mol Life Sci"},{"key":"B8","doi-asserted-by":"publisher","first-page":"223","DOI":"10.1186\/s13075-016-1123-x","article-title":"The complement system is activated in synovial fluid from subjects with knee injury and from patients with osteoarthritis","volume":"18","author":"Struglics","year":"2016","journal-title":"Arthritis Res Ther"},{"key":"B9","doi-asserted-by":"publisher","DOI":"10.18632\/aging.103286","article-title":"Modelling biological age based on plasma peptides in Han Chinese adults","volume":"12","author":"Cao","year":"2020","journal-title":"Aging (Albany NY)"},{"key":"B10","doi-asserted-by":"publisher","DOI":"10.1038\/s41423-020-0386-y","article-title":"Centenarian longevity is positively correlated with IgE levels but negatively correlated with C3\/C4 levels, abdominal obesity and metabolic syndrome","volume":"17","author":"Fu","year":"2020","journal-title":"Cell Mol Immunol"},{"key":"B11","doi-asserted-by":"publisher","DOI":"10.1038\/s41577-023-00926-1","article-title":"A guide to complement biology, pathology and therapeutic opportunity","volume":"24","author":"Mastellos","year":"2024","journal-title":"Nat Rev Immunol"},{"key":"B12","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2015.00262","article-title":"Complement system part I - molecular mechanisms of activation and regulation","volume":"6","author":"Merle","year":"2015","journal-title":"Front Immunol"},{"key":"B13","doi-asserted-by":"publisher","first-page":"70","DOI":"10.1186\/s12979-024-00475-8","article-title":"Association between serum IgM and all-cause mortality risk in Chinese centenarians: a prospective cohort study","volume":"21","author":"Zhang","year":"2024","journal-title":"Immun Ageing"},{"key":"B14","doi-asserted-by":"publisher","first-page":"24","DOI":"10.1186\/s12979-025-00520-0","article-title":"Associations of serum total light chain kappa and lambda levels with all-cause mortality in Chinese centenarians","volume":"22","author":"Duan","year":"2025","journal-title":"Immun Ageing"},{"key":"B15","doi-asserted-by":"publisher","first-page":"383","DOI":"10.1038\/nrneph.2016.70","article-title":"Complement in disease: a defence system turning offensive","volume":"12","author":"Ricklin","year":"2016","journal-title":"Nat Rev Nephrol"},{"key":"B16","doi-asserted-by":"publisher","first-page":"34","DOI":"10.1038\/cr.2009.139","article-title":"Complement and its role in innate and adaptive immune responses","volume":"20","author":"Dunkelberger","year":"2010","journal-title":"Cell Res"},{"key":"B17","doi-asserted-by":"publisher","first-page":"33","DOI":"10.1515\/jtim-2025-0005","article-title":"Senescent cells as a target for anti-aging interventions: From senolytics to immune therapies","volume":"13","author":"Fu","year":"2025","journal-title":"J Transl Int Med"},{"key":"B18","doi-asserted-by":"publisher","first-page":"12","DOI":"10.1016\/j.neurobiolaging.2016.12.017","article-title":"A review of human diseases caused or exacerbated by aberrant complement activation","volume":"52","author":"McGeer","year":"2017","journal-title":"Neurobiol Aging"},{"key":"B19","doi-asserted-by":"publisher","first-page":"63","DOI":"10.1186\/s13075-021-02433-x","article-title":"Serum complement 3 is a potential biomarker for assessing disease activity in Takayasu arteritis","volume":"23","author":"Chen","year":"2021","journal-title":"Arthritis Res Ther"},{"key":"B20","doi-asserted-by":"publisher","DOI":"10.1007\/s40620-023-01683-z","article-title":"Low levels of complement factor C3 at diagnosis can predict outcome in antineutrophil antibody associated vasculitis","volume":"36","author":"Scurt","year":"2023","journal-title":"J Nephrol"},{"key":"B21","doi-asserted-by":"publisher","DOI":"10.1177\/09612033231164091","article-title":"Hospitalized patients with positive antiphospholipid antibodies who have low complement levels are at increased risk for death-a retrospective cohort study","volume":"32","author":"Itelman","year":"2023","journal-title":"Lupus"},{"key":"B22","doi-asserted-by":"publisher","DOI":"10.2147\/ijgm.S348519","article-title":"Association of complement C3 with clinical deterioration among hospitalized patients with COVID-19","volume":"15","author":"Jiang","year":"2022","journal-title":"Int J Gen Med"},{"key":"B23","doi-asserted-by":"publisher","DOI":"10.1097\/01.hjr.0000244582.30421.b2","article-title":"Complement C3 and C4 in plasma and incidence of myocardial infarction and stroke: a population-based cohort study","volume":"14","author":"Engstr\u00f6m","year":"2007","journal-title":"Eur J Cardiovasc Prev Rehabil"},{"key":"B24","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1911999117","article-title":"Sex differences in adult lifespan and aging rates of mortality across wild mammals","volume":"117","author":"Lema\u00eetre","year":"2020","journal-title":"Proc Natl Acad Sci USA"},{"key":"B25","doi-asserted-by":"publisher","DOI":"10.1210\/endrev\/bnac017","article-title":"Estrogen receptor signaling in the immune system","volume":"44","author":"Chakraborty","year":"2023","journal-title":"Endocr Rev"},{"key":"B26","doi-asserted-by":"publisher","DOI":"10.1038\/s41581-023-00704-1","article-title":"Complosome - the intracellular complement system","volume":"19","author":"West","year":"2023","journal-title":"Nat Rev Nephrol"},{"key":"B27","doi-asserted-by":"publisher","DOI":"10.1146\/annurev-immunol-032713-120154","article-title":"Complement and its receptors: new insights into human disease","volume":"32","author":"Holers","year":"2014","journal-title":"Annu Rev Immunol"},{"key":"B28","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2024.02.010","article-title":"Complement-ary protection for all ages","volume":"57","author":"Han","year":"2024","journal-title":"Immunity"},{"key":"B29","doi-asserted-by":"publisher","DOI":"10.1038\/s41577-026-01291-5","article-title":"The long-lived immune system of centenarians","author":"Plaza-Florido","year":"2026","journal-title":"Nat Rev Immunol"},{"key":"B30","doi-asserted-by":"publisher","DOI":"10.1515\/jtim-2026-0043","article-title":"Inflammation, metabolism, and aging in heart failure with preserved ejection fraction: Mechanisms and treatment perspectives","volume":"14","author":"Teng","year":"2026","journal-title":"J Transl Int Med"},{"key":"B31","doi-asserted-by":"publisher","DOI":"10.2174\/1573399814666180417122030","article-title":"Complement components, C3 and C4, and the metabolic syndrome","volume":"15","author":"Copenhaver","year":"2019","journal-title":"Curr Diabetes Rev"},{"key":"B32","doi-asserted-by":"publisher","DOI":"10.2337\/dc07-0637","article-title":"Serum C3 is a stronger inflammatory marker of insulin resistance than C-reactive protein, leukocyte count, and erythrocyte sedimentation rate: comparison study in an elderly population","volume":"30","author":"Muscari","year":"2007","journal-title":"Diabetes Care"},{"key":"B33","doi-asserted-by":"publisher","DOI":"10.1016\/j.clnu.2023.04.023","article-title":"Association between different adiposity measures and all-cause mortality risk among centenarians: A prospective cohort study","volume":"42","author":"Liu","year":"2023","journal-title":"Clin Nutr"}],"container-title":["Frontiers in Immunology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fimmu.2026.1911948\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,9,9]],"date-time":"2026-09-09T04:42:04Z","timestamp":1788928924000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fimmu.2026.1911948\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,9,9]]},"references-count":33,"alternative-id":["10.3389\/fimmu.2026.1911948"],"URL":"https:\/\/doi.org\/10.3389\/fimmu.2026.1911948","relation":{},"ISSN":["1664-3224"],"issn-type":[{"value":"1664-3224","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,9,9]]},"article-number":"1911948"}}