{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,1]],"date-time":"2026-07-01T20:46:12Z","timestamp":1782938772797,"version":"3.54.5"},"reference-count":53,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2026,5,21]],"date-time":"2026-05-21T00:00:00Z","timestamp":1779321600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,5,21]],"date-time":"2026-05-21T00:00:00Z","timestamp":1779321600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Aging Cell"],"published-print":{"date-parts":[[2026,6]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>In this cross\u2010sectional cohort we analyzed data from 4260 \u201chealth enthusiasts\u201d who purchased at least one saliva\u2010based DNA epigenetic test between 2020 and 2025 and completed detailed lifestyle and supplement questionnaires. A proprietary 9\u2010CpG clock with a mean absolute error of 5.4\u2009years served as the primary biomarker of biological age. High prevalence (71%) of supplement use in this cohort increased our power to study the effects of supplements compared to earlier studies that focused on the general population. We tested the association between 84 commonly used supplements and biological age measured as Age Residual. In our cross\u2010sectional analysis, a commercially available, delayed\u2010release calcium\u2010alpha\u2010ketoglutarate (dAKG)\u2009+\u2009vitamin supplement (\u201cRejuvant\u201d) was associated with an average 1.8\u2010year lower Age Residual. The difference remained significant in models adjusted for age, sex, smoking, health status and additional covariates. In contrast, participants who reported taking regular AKG showed a much smaller and statistically insignificant benefit. Among medications, there was a non\u2010significant benefit of antihistamine use, although the analysis was sample\u2010size limited. In a longitudinal subset, intake of coenzyme Q10 (CoQ10) and dAKG was associated with increased odds of a lower Age Residual, but the results were not significant after multivariate correction. In conclusion, this study underscores the utility of an inexpensive saliva\u2010based epigenetic test for population\u2010level aging research and the benefits of health enthusiast cohorts. It highlights AKG and CoQ10, among others, as promising supplements warranting further investigation. Limitations like healthy user and recruitment bias remain and will require future controlled trials to fully address.<\/jats:p>","DOI":"10.1111\/acel.70517","type":"journal-article","created":{"date-parts":[[2026,5,21]],"date-time":"2026-05-21T20:24:03Z","timestamp":1779395043000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Supplements and Drugs Are Associated With Biological Age in a Cohort of Exceptionally Healthy Individuals"],"prefix":"10.1111","volume":"25","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1120-3079","authenticated-orcid":false,"given":"Kamil","family":"Pabis","sequence":"first","affiliation":[{"name":"Healthy Longevity Translational Research Programme, Yong Loo Lin School of Medicine National University of Singapore  Singapore City Singapore"},{"name":"Department of Biochemistry, Yong Loo Lin School of Medicine National University of Singapore  Singapore City Singapore"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Weilan","family":"Wang","sequence":"additional","affiliation":[{"name":"Healthy Longevity Translational Research Programme, Yong Loo Lin School of Medicine National University of Singapore  Singapore City Singapore"},{"name":"NUS Academy for Healthy Longevity, Yong Loo Lin School of Medicine National University of Singapore  Singapore City Singapore"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kumar","family":"Selvarajoo","sequence":"additional","affiliation":[{"name":"Bioinformatics Institute (BII), Agency for Science Technology and Research (A*STAR)  Singapore City Singapore"},{"name":"Synthetic Biology for Clinical and Technological Innovation (SynCTI) National University of Singapore (NUS)  Singapore City Singapore"},{"name":"School of Biological Sciences Nanyang Technological University (NTU)  Singapore City Singapore"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yelena V.","family":"Budovskaya","sequence":"additional","affiliation":[{"name":"TruMe Inc.  Alameda California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vincenzo","family":"Sorrentino","sequence":"additional","affiliation":[{"name":"Healthy Longevity Translational Research Programme, Yong Loo Lin School of Medicine National University of Singapore  Singapore City Singapore"},{"name":"Department of Biochemistry, Yong Loo Lin School of Medicine National University of Singapore  Singapore City Singapore"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jan","family":"Gruber","sequence":"additional","affiliation":[{"name":"Healthy Longevity Translational Research Programme, Yong Loo Lin School of Medicine National University of Singapore  Singapore City Singapore"},{"name":"Department of Biochemistry, Yong Loo Lin School of Medicine National University of Singapore  Singapore City Singapore"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Brian K.","family":"Kennedy","sequence":"additional","affiliation":[{"name":"Healthy Longevity Translational Research Programme, Yong Loo Lin School of Medicine National University of Singapore  Singapore City Singapore"},{"name":"Department of Biochemistry, Yong Loo Lin School of Medicine National University of Singapore  Singapore City Singapore"},{"name":"Department of Physiology, Yong Loo Lin School of Medicine National University of Singapore  Singapore City Singapore"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,5,21]]},"reference":[{"key":"e_1_2_13_2_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10654\u2010012\u20109714\u20106"},{"key":"e_1_2_13_3_1","doi-asserted-by":"publisher","DOI":"10.7554\/eLife.73420"},{"key":"e_1_2_13_4_1","doi-asserted-by":"publisher","DOI":"10.1038\/s43587\u2010024\u201000793\u2010y"},{"key":"e_1_2_13_5_1","doi-asserted-by":"publisher","DOI":"10.1159\/000212330"},{"key":"e_1_2_13_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.maturitas.2024.107998"},{"key":"e_1_2_13_7_1","unstructured":"Clarke T. C. L. I.Black B. J.Stussman P. M.Barnes andR. L.Nahin.2015. \u201cTrends in the Use of Complementary Health Approaches Among Adults: United States 2002\u20132012.\u201d National Health Statistics Reports (79) 1\u201316."},{"key":"e_1_2_13_8_1","doi-asserted-by":"publisher","DOI":"10.18632\/aging.101021"},{"key":"e_1_2_13_9_1","doi-asserted-by":"publisher","DOI":"10.1002\/arch.22116"},{"key":"e_1_2_13_10_1","doi-asserted-by":"publisher","DOI":"10.18632\/aging.203736"},{"key":"e_1_2_13_11_1","doi-asserted-by":"publisher","DOI":"10.1038\/s43587\u2010024\u201000646\u20108"},{"key":"e_1_2_13_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.tranon.2021.101029"},{"key":"e_1_2_13_13_1","doi-asserted-by":"publisher","DOI":"10.18632\/aging.101626"},{"key":"e_1_2_13_14_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1532\u20105415.2011.03721.x"},{"key":"e_1_2_13_15_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.tem.2021.11.003"},{"key":"e_1_2_13_16_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12986\u2010023\u201000753\u20100"},{"key":"e_1_2_13_17_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10522\u2010025\u201010265\u20104"},{"key":"e_1_2_13_18_1","doi-asserted-by":"publisher","DOI":"10.1007\/BF02535072"},{"key":"e_1_2_13_19_1","doi-asserted-by":"publisher","DOI":"10.18632\/aging.203115"},{"key":"e_1_2_13_20_1","doi-asserted-by":"publisher","DOI":"10.18632\/aging.101414"},{"key":"e_1_2_13_21_1","doi-asserted-by":"publisher","DOI":"10.1136\/annrheumdis\u20102020\u2010217176"},{"key":"e_1_2_13_22_1","doi-asserted-by":"publisher","DOI":"10.1136\/bmj.m456"},{"key":"e_1_2_13_23_1","doi-asserted-by":"publisher","DOI":"10.1210\/clinem\/dgac585"},{"key":"e_1_2_13_24_1","doi-asserted-by":"publisher","DOI":"10.1080\/15216549800201772"},{"key":"e_1_2_13_25_1","doi-asserted-by":"publisher","DOI":"10.1111\/acel.14132"},{"key":"e_1_2_13_26_1","doi-asserted-by":"publisher","DOI":"10.1136\/bmj.l1628"},{"key":"e_1_2_13_27_1","doi-asserted-by":"publisher","DOI":"10.1093\/gerona\/gly060"},{"key":"e_1_2_13_28_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11357\u2010024\u201001176\u20102"},{"key":"e_1_2_13_29_1","doi-asserted-by":"publisher","DOI":"10.1111\/acel.14334"},{"key":"e_1_2_13_30_1","doi-asserted-by":"publisher","DOI":"10.1001\/archinternmed.2011.445"},{"key":"e_1_2_13_31_1","doi-asserted-by":"publisher","DOI":"10.1101\/cshperspect.a025940"},{"key":"e_1_2_13_32_1","doi-asserted-by":"publisher","DOI":"10.1001\/jamainternmed.2013.6473"},{"key":"e_1_2_13_33_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.arr.2024.102512"},{"key":"e_1_2_13_34_1","doi-asserted-by":"publisher","DOI":"10.1097\/HJH.0000000000003874"},{"key":"e_1_2_13_35_1","doi-asserted-by":"crossref","unstructured":"Pilley S. E. D.Awad D.Latumalea et\u00a0al.2024.\u201cA Metabolic Atlas of Mouse Aging.\u201dhttps:\/\/doi.org\/10.1101\/2024.05.04.592445.","DOI":"10.1101\/2024.05.04.592445"},{"key":"e_1_2_13_36_1","doi-asserted-by":"publisher","DOI":"10.2188\/jea.JE20210393"},{"key":"e_1_2_13_37_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11357\u2010023\u201000813\u20106"},{"key":"e_1_2_13_38_1","doi-asserted-by":"crossref","unstructured":"Sehgal R. D.Borrus J.Kasamato et\u00a0al.2024. \u201cDNAm Aging Biomarkers Community Community Longevity Interventional Studies & Higgins\u2010Chen A. (2024). DNAm Aging Biomarkers Are Responsive: Insights From 51 Longevity Interventional Studies in Humans.\u201dbioRxiv: The Preprint Server for Biology.https:\/\/doi.org\/10.1101\/2024.10.22.619522.","DOI":"10.1101\/2024.10.22.619522"},{"key":"e_1_2_13_39_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cmet.2020.08.004"},{"key":"e_1_2_13_40_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.freeradbiomed.2005.08.037"},{"key":"e_1_2_13_41_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1474\u20109726.2008.00414.x"},{"key":"e_1_2_13_42_1","doi-asserted-by":"publisher","DOI":"10.1111\/acel.13724"},{"key":"e_1_2_13_43_1","doi-asserted-by":"publisher","DOI":"10.1002\/cam4.2862"},{"key":"e_1_2_13_44_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11357\u2010023\u201000784\u20108"},{"key":"e_1_2_13_45_1","doi-asserted-by":"publisher","DOI":"10.4235\/agmr.24.0034"},{"key":"e_1_2_13_46_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11357\u2010022\u201000581\u20109"},{"key":"e_1_2_13_47_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10522\u2010022\u201009956\u2010z"},{"key":"e_1_2_13_48_1","doi-asserted-by":"publisher","DOI":"10.1093\/aje\/152.2.149"},{"key":"e_1_2_13_49_1","doi-asserted-by":"publisher","DOI":"10.1038\/ncomms4563"},{"key":"e_1_2_13_50_1","doi-asserted-by":"publisher","DOI":"10.1001\/jamainternmed.2013.3283"},{"key":"e_1_2_13_51_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12872\u2010024\u201004232\u2010z"},{"key":"e_1_2_13_52_1","doi-asserted-by":"publisher","DOI":"10.1093\/ajh\/hpx084"},{"key":"e_1_2_13_53_1","doi-asserted-by":"publisher","DOI":"10.1038\/s44324\u2010025\u201000067\u20100"},{"key":"e_1_2_13_54_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13148\u2010025\u201001868\u20102"}],"container-title":["Aging Cell"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/acel.70517","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1111\/acel.70517","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/acel.70517","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,7,1]],"date-time":"2026-07-01T20:26:16Z","timestamp":1782937576000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/acel.70517"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,5,21]]},"references-count":53,"journal-issue":{"issue":"6","published-print":{"date-parts":[[2026,6]]}},"alternative-id":["10.1111\/acel.70517"],"URL":"https:\/\/doi.org\/10.1111\/acel.70517","archive":["Portico"],"relation":{},"ISSN":["1474-9718","1474-9726"],"issn-type":[{"value":"1474-9718","type":"print"},{"value":"1474-9726","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,5,21]]},"assertion":[{"value":"2025-09-21","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-04-16","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-05-21","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e70517"}}