{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,2]],"date-time":"2026-06-02T09:59:09Z","timestamp":1780394349693,"version":"3.54.1"},"reference-count":27,"publisher":"Public Library of Science (PLoS)","issue":"3","license":[{"start":{"date-parts":[[2026,3,2]],"date-time":"2026-03-02T00:00:00Z","timestamp":1772409600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Suzhou Science and Technology Development Program","award":["SYW2024048"],"award-info":[{"award-number":["SYW2024048"]}]},{"name":"Key Disciplines of Changshu","award":["CSZDXK202303"],"award-info":[{"award-number":["CSZDXK202303"]}]},{"name":"Innovative Research Program of Xiangyang No.1 People\u2019s Hospital","award":["XYY2025ON21"],"award-info":[{"award-number":["XYY2025ON21"]}]}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS One"],"abstract":"\n Objective<\/jats:title>\n Aging is characterized by progressive physiological and psychological changes, leading to decreased cellular metabolism and increased vulnerability to age-related diseases.<\/jats:p>\n <\/jats:sec>\n \n Methods.<\/jats:title>\n In this study, we examined the relationship between circulating Klotho levels and biological age acceleration (BAA) in a representative cohort of middle-aged and older adults. Data were obtained from the National Health and Nutrition Examination Survey (NHANES, 2007\u20132010), including 5,654 participants aged 45\u201385 years. Serum Klotho concentrations were quantified using ELISA, while biological age was estimated with the BioAge R package.<\/jats:p>\n <\/jats:sec>\n \n Result<\/jats:title>\n Linear regression analyses demonstrated a robust inverse association between log-transformed Klotho levels and BAA across all statistical models, with reductions of \u22121.06 (95% CI: \u22121.77 to \u22120.36, p\u2009=\u20090.005), \u22121.44 (95% CI: \u22122.15 to \u22120.73, p\u2009<\u20090.001), and \u22121.30 (95% CI: \u22122.20 to \u22120.40, p\u2009=\u20090.01). Consistent results were observed in logistic regression models, where higher Klotho concentrations were linked to lower odds of accelerated aging (OR = 0.72, 95% CI: 0.59\u20130.88, p\u2009=\u20090.002; OR = 0.63, 95% CI: 0.51\u20130.77, p\u2009<\u20090.0001; OR = 0.62, 95% CI: 0.46\u20130.84, p\u2009=\u20090.01). Subgroup analyses revealed significant associations in women, participants over 60 years of age, and individuals without chronic illnesses. Interaction analyses further indicated that age (p-interaction\u2009=\u20090.002), alcohol intake (p-interaction\u2009=\u20090.04), and diabetes status (p-interaction\u2009=\u20090.03) significantly modified the Klotho\u2013BAA relationship. Moreover, restricted cubic spline analysis showed a non-linear L-shaped dose-response pattern, suggesting that the protective effect of Klotho becomes more pronounced above a certain threshold.<\/jats:p>\n <\/jats:sec>\n \n Conclusion<\/jats:title>\n Collectively, these findings underscore the pivotal role of Klotho in the biology of aging and emphasize the importance of accounting for demographic and health-related modifiers in future investigations.<\/jats:p>\n <\/jats:sec>","DOI":"10.1371\/journal.pone.0343429","type":"journal-article","created":{"date-parts":[[2026,3,2]],"date-time":"2026-03-02T18:26:11Z","timestamp":1772475971000},"page":"e0343429","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":1,"title":["Klotho levels and biological age acceleration: Insights from a diverse cohort of middle-aged and elderly individuals"],"prefix":"10.1371","volume":"21","author":[{"given":"Mengna","family":"Huang","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guoxin","family":"Huang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chaoshen","family":"Wu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lei","family":"Zhu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bin","family":"Pei","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hongwei","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6062-8161","authenticated-orcid":true,"given":"Da","family":"Qian","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Puzhao","family":"Wu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2026,3,2]]},"reference":[{"key":"pone.0343429.ref001","doi-asserted-by":"crossref","first-page":"101536","DOI":"10.1016\/j.arr.2021.101536","article-title":"The accelerated aging phenotype: The role of race and social determinants of health on aging","volume":"73","author":"N Noren Hooten","year":"2022","journal-title":"Ageing Res Rev"},{"key":"pone.0343429.ref002","doi-asserted-by":"crossref","first-page":"469580221121511","DOI":"10.1177\/00469580221121511","article-title":"Economic implications of health care burden for elderly population","volume":"59","author":"B Tang","year":"2022","journal-title":"Inquiry"},{"issue":"6655","key":"pone.0343429.ref003","doi-asserted-by":"crossref","first-page":"45","DOI":"10.1038\/36285","article-title":"Mutation of the mouse klotho gene leads to a syndrome resembling ageing","volume":"390","author":"M Kuro-o","year":"1997","journal-title":"Nature"},{"key":"pone.0343429.ref004","doi-asserted-by":"crossref","first-page":"139234","DOI":"10.1016\/j.ijbiomac.2024.139234","article-title":"Klotho protein: A key modulator of aging and COVID-19 severity","volume":"296","author":"K Shahzamani","year":"2025","journal-title":"Int J Biol Macromol"},{"key":"pone.0343429.ref005","doi-asserted-by":"crossref","first-page":"102730","DOI":"10.1016\/j.pmedr.2024.102730","article-title":"The prognostic value of serum \u03b1-klotho in age-related diseases among the US population: A prospective population-based cohort study","volume":"42","author":"Z Yang","year":"2024","journal-title":"Prev Med Rep"},{"key":"pone.0343429.ref006","doi-asserted-by":"crossref","first-page":"1415494","DOI":"10.3389\/fnagi.2024.1415494","article-title":"The role of serum \u03b1-Klotho levels in preventing hearing impairment among middle-aged and older adults: insights from a nationally representative sample","volume":"16","author":"S Wang","year":"2024","journal-title":"Front Aging Neurosci"},{"key":"pone.0343429.ref007","doi-asserted-by":"crossref","first-page":"101766","DOI":"10.1016\/j.arr.2022.101766","article-title":"Aging-suppressor Klotho: Prospects in diagnostics and therapeutics","volume":"82","author":"CR Abraham","year":"2022","journal-title":"Ageing Res Rev"},{"issue":"12","key":"pone.0343429.ref008","doi-asserted-by":"crossref","first-page":"2744","DOI":"10.3390\/nu15122744","article-title":"Serum anti-aging protein \u03b1-klotho mediates the association between diet quality and kidney function","volume":"15","author":"Q Cai","year":"2023","journal-title":"Nutrients"},{"issue":"6","key":"pone.0343429.ref009","doi-asserted-by":"crossref","first-page":"2795","DOI":"10.1007\/s11357-021-00480-5","article-title":"A toolkit for quantification of biological age from blood chemistry and organ function test data: BioAge","volume":"43","author":"D Kwon","year":"2021","journal-title":"Geroscience"},{"issue":"1","key":"pone.0343429.ref010","doi-asserted-by":"crossref","first-page":"243","DOI":"10.1007\/s00394-023-03261-2","article-title":"Relationship between dietary macronutrients intake and biological aging: a cross-sectional analysis of NHANES data","volume":"63","author":"X Zhu","year":"2024","journal-title":"Eur J Nutr"},{"issue":"1","key":"pone.0343429.ref011","doi-asserted-by":"crossref","first-page":"337","DOI":"10.1038\/s41398-023-02632-x","article-title":"Relationship of Klotho with cognition and dementia: Results from the NHANES 2011-2014 and Mendelian randomization study","volume":"13","author":"Y Wu","year":"2023","journal-title":"Transl Psychiatry"},{"key":"pone.0343429.ref012","doi-asserted-by":"crossref","first-page":"8821292","DOI":"10.1155\/2021\/8821292","article-title":"FGF23: A review of its role in mineral metabolism and renal and cardiovascular disease","volume":"2021","author":"A Kurpas","year":"2021","journal-title":"Dis Markers"},{"key":"pone.0343429.ref013","doi-asserted-by":"crossref","first-page":"711904","DOI":"10.3389\/fphys.2021.711904","article-title":"Correlation between soluble klotho and vascular calcification in chronic kidney disease: a meta-analysis and systematic review","volume":"12","author":"Q Liu","year":"2021","journal-title":"Frontiers in Physiology"},{"key":"pone.0343429.ref014","doi-asserted-by":"crossref","first-page":"117719","DOI":"10.1016\/j.biopha.2024.117719","article-title":"Roles of Lysyl oxidases (LOX(L)) in pathologic calcification","volume":"181","author":"E Faure","year":"2024","journal-title":"Biomed Pharmacother"},{"issue":"17","key":"pone.0343429.ref015","doi-asserted-by":"crossref","first-page":"1413","DOI":"10.3390\/cells13171413","article-title":"Anti-Inflammatory Role of the Klotho Protein and Relevance to Aging","volume":"13","author":"GJ Prud\u2019homme","year":"2024","journal-title":"Cells"},{"key":"pone.0343429.ref016","doi-asserted-by":"crossref","first-page":"101465","DOI":"10.1016\/j.arr.2021.101465","article-title":"Principles of brain aging: Status and challenges of modeling human molecular changes in mice","volume":"72","author":"V Kluever","year":"2021","journal-title":"Ageing Res Rev"},{"issue":"1","key":"pone.0343429.ref017","doi-asserted-by":"crossref","first-page":"20312","DOI":"10.1038\/s41598-023-47686-5","article-title":"Klotho inhibits IGF1R\/PI3K\/AKT signalling pathway and protects the heart from oxidative stress during ischemia\/reperfusion injury","volume":"13","author":"A Olejnik","year":"2023","journal-title":"Sci Rep"},{"issue":"8","key":"pone.0343429.ref018","doi-asserted-by":"crossref","first-page":"931","DOI":"10.1038\/s43587-023-00441-x","article-title":"Longevity factor klotho enhances cognition in aged nonhuman primates","volume":"3","author":"SA Castner","year":"2023","journal-title":"Nat Aging"},{"issue":"1","key":"pone.0343429.ref019","doi-asserted-by":"crossref","first-page":"245","DOI":"10.1186\/s12877-024-04661-7","article-title":"Serum soluble alpha-klotho klotho and cognitive functioning in older adults aged 60 and 79: an analysis of cross-sectional data of the National Health and Nutrition Examination Survey 2011 to 2014","volume":"24","author":"S Ge","year":"2024","journal-title":"BMC Geriatr"},{"key":"pone.0343429.ref020","doi-asserted-by":"crossref","first-page":"115545","DOI":"10.1016\/j.bbr.2025.115545","article-title":"Molecular mechanisms of neuroprotection: The interplay of Klotho, SIRT-1, Nrf2, and HO-1 in neurological health","volume":"485","author":"R Rana","year":"2025","journal-title":"Behav Brain Res"},{"issue":"1","key":"pone.0343429.ref021","doi-asserted-by":"crossref","first-page":"5712","DOI":"10.1038\/s41598-024-56377-8","article-title":"Role of klotho and fibroblast growth factor 23 in arterial calcification, thickness, and stiffness: a meta-analysis of observational studies","volume":"14","author":"CDK Wungu","year":"2024","journal-title":"Sci Rep"},{"issue":"12","key":"pone.0343429.ref022","first-page":"2342","article-title":"Unclean cooking fuel use and health outcomes in older adults: potential mechanisms, public health implications, and future directions","volume":"78","author":"L Smith","year":"2023","journal-title":"The Journals of Gerontology: Series A"},{"key":"pone.0343429.ref023","doi-asserted-by":"crossref","first-page":"27","DOI":"10.1016\/j.freeradbiomed.2020.11.027","article-title":"Human CREBBP acetyltransferase is impaired by etoposide quinone, an oxidative and leukemogenic metabolite of the anticancer drug etoposide through modification of redox-sensitive zinc-finger cysteine residues","volume":"162","author":"W Zhang","year":"2021","journal-title":"Free Radic Biol Med"},{"issue":"1","key":"pone.0343429.ref024","doi-asserted-by":"crossref","first-page":"17587","DOI":"10.1038\/s41598-022-22123-1","article-title":"A systematic review and meta-analysis demonstrating Klotho as an emerging exerkine","volume":"12","author":"L Corr\u00eaa H de","year":"2022","journal-title":"Sci Rep"},{"issue":"1","key":"pone.0343429.ref025","doi-asserted-by":"crossref","first-page":"685","DOI":"10.1186\/s12967-025-06685-y","article-title":"Acute effects of a single bout of high-intensity strength and endurance exercise on cognitive biomarkers in young adults and elderly men: a within-subjects crossover study","volume":"23","author":"CH Bekkos","year":"2025","journal-title":"J Transl Med"},{"issue":"1","key":"pone.0343429.ref026","doi-asserted-by":"crossref","first-page":"76","DOI":"10.1038\/s41392-025-02145-7","article-title":"Antiageing strategy for neurodegenerative diseases: from mechanisms to clinical advances","volume":"10","author":"Q Jiang","year":"2025","journal-title":"Signal Transduct Target Ther"},{"issue":"1","key":"pone.0343429.ref027","doi-asserted-by":"crossref","DOI":"10.1093\/ckj\/sfad276","article-title":"Klotho: a potential therapeutic target in aging and neurodegeneration beyond chronic kidney disease-a comprehensive review from the ERA CKD-MBD working group","volume":"17","author":"M Kanbay","year":"2023","journal-title":"Clin Kidney J"}],"container-title":["PLOS One"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pone.0343429","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,3,2]],"date-time":"2026-03-02T18:26:15Z","timestamp":1772475975000},"score":1,"resource":{"primary":{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pone.0343429"}},"subtitle":[],"editor":[{"given":"Ian James","family":"Martins","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"editor"}]}],"short-title":[],"issued":{"date-parts":[[2026,3,2]]},"references-count":27,"journal-issue":{"issue":"3","published-online":{"date-parts":[[2026,3,2]]}},"URL":"https:\/\/doi.org\/10.1371\/journal.pone.0343429","relation":{},"ISSN":["1932-6203"],"issn-type":[{"value":"1932-6203","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,3,2]]}}}