{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,21]],"date-time":"2026-10-21T19:46:14Z","timestamp":1792611974394,"version":"4.5.0"},"reference-count":38,"publisher":"Wiley","issue":"10","license":[{"start":{"date-parts":[[2026,10,8]],"date-time":"2026-10-08T00:00:00Z","timestamp":1791417600000},"content-version":"vor","delay-in-days":7,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T00:00:00Z","timestamp":1790812800000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/100000049","name":"National Institute on Aging","doi-asserted-by":"publisher","award":["R01AG060110"],"award-info":[{"award-number":["R01AG060110"]}],"id":[{"id":"10.13039\/100000049","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000049","name":"National Institute on Aging","doi-asserted-by":"publisher","award":["R01AG065403"],"award-info":[{"award-number":["R01AG065403"]}],"id":[{"id":"10.13039\/100000049","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000049","name":"National Institute on Aging","doi-asserted-by":"publisher","award":["T32AG019134"],"award-info":[{"award-number":["T32AG019134"]}],"id":[{"id":"10.13039\/100000049","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Aging Cell"],"published-print":{"date-parts":[[2026,10]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>Epigenetic clocks have emerged as potential biomarkers of aging due to their association with morbidity and mortality. They have recently gained traction as outcome measurements for anti\u2010aging interventions. However, as the number of new epigenetic clocks continues to grow, different clocks may not agree on the effect of an intervention. This raises the question of when researchers can trust epigenetic clock results. In this study, we find that when extending previously published single\u2010clock intervention studies to include additional clock models, no additional clocks reach statistical significance. We then analyze clock behavior across positive control datasets (age\u2010accelerating events) to propose three criteria that increase confidence in a result: (1) reliable PC\u2010based clocks respond, (2) mortality\u2010trained or pace\u2010of\u2010aging clocks respond, and (3) multiple clocks respond in the same direction. To explain why genuine effects would appear across multiple clocks, we perform a simulation study to demonstrate how reliable clocks are more sensitive to true effects, and use longitudinal control datasets to show that reliable clock changes are correlated with each other. We then show examples of interventions that do satisfy these criteria. These findings provide a framework for interpreting epigenetic clock results in anti\u2010aging intervention studies, and suggest that some previously published single\u2010clock findings may warrant reexamination.<\/jats:p>","DOI":"10.1111\/acel.70756","type":"journal-article","created":{"date-parts":[[2026,10,9]],"date-time":"2026-10-09T04:18:04Z","timestamp":1791519484000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["When to Trust Epigenetic Clocks: Avoiding False Positives in Aging Interventions"],"prefix":"10.1111","volume":"25","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1493-0896","authenticated-orcid":false,"given":"Daniel S.","family":"Borrus","sequence":"first","affiliation":[{"name":"Department of Psychiatry Yale University School of Medicine  New Haven Connecticut USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9387-1758","authenticated-orcid":false,"given":"Raghav","family":"Sehgal","sequence":"additional","affiliation":[{"name":"Department of Psychiatry Yale University School of Medicine  New Haven Connecticut USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jenel Fraij","family":"Armstrong","sequence":"additional","affiliation":[{"name":"Program in Computational Biology and Bioinformatics Yale University  New Haven Connecticut USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4604-6093","authenticated-orcid":false,"given":"Jessica","family":"Kasamoto","sequence":"additional","affiliation":[{"name":"Program in Computational Biology and Bioinformatics Yale University  New Haven Connecticut USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1020-8783","authenticated-orcid":false,"given":"John","family":"Gonzalez","sequence":"additional","affiliation":[{"name":"Department of Pathology Yale University School of Medicine  New Haven Connecticut USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2904-2741","authenticated-orcid":false,"given":"Albert","family":"Higgins\u2010Chen","sequence":"additional","affiliation":[{"name":"Department of Psychiatry Yale University School of Medicine  New Haven Connecticut USA"},{"name":"Department of Pathology Yale University School of Medicine  New Haven Connecticut USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,10,8]]},"reference":[{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11427-023-2305-0"},{"key":"e_1_2_10_3_1","doi-asserted-by":"publisher","DOI":"10.7554\/eLife.54870"},{"key":"e_1_2_10_4_1","doi-asserted-by":"publisher","DOI":"10.7554\/eLife.73420"},{"key":"e_1_2_10_5_1","doi-asserted-by":"publisher","DOI":"10.1101\/2025.10.16.682960"},{"key":"e_1_2_10_6_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-017-06847-z"},{"key":"e_1_2_10_7_1","doi-asserted-by":"publisher","DOI":"10.1111\/acel.13696"},{"key":"e_1_2_10_8_1","doi-asserted-by":"publisher","DOI":"10.1080\/02701367.2023.2228388"},{"key":"e_1_2_10_9_1","doi-asserted-by":"publisher","DOI":"10.1038\/d41586-022-00077-8"},{"key":"e_1_2_10_10_1","doi-asserted-by":"publisher","DOI":"10.18632\/aging.202913"},{"key":"e_1_2_10_11_1","doi-asserted-by":"publisher","DOI":"10.1158\/1055-9965.EPI-14-0767"},{"key":"e_1_2_10_12_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11357-019-00149-0"},{"key":"e_1_2_10_13_1","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCULATIONAHA.117.030501"},{"key":"e_1_2_10_14_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.molcel.2012.10.016"},{"key":"e_1_2_10_15_1","doi-asserted-by":"publisher","DOI":"10.1038\/s43587-022-00248-2"},{"key":"e_1_2_10_16_1","doi-asserted-by":"publisher","DOI":"10.1186\/gb-2013-14-10-r115"},{"key":"e_1_2_10_17_1","doi-asserted-by":"publisher","DOI":"10.18632\/aging.101508"},{"key":"e_1_2_10_18_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41576-018-0004-3"},{"key":"e_1_2_10_19_1","doi-asserted-by":"publisher","DOI":"10.18632\/aging.101414"},{"key":"e_1_2_10_20_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2022.11.001"},{"key":"e_1_2_10_21_1","doi-asserted-by":"publisher","DOI":"10.18632\/aging.101684"},{"key":"e_1_2_10_22_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13073-023-01211-5"},{"key":"e_1_2_10_23_1","doi-asserted-by":"publisher","DOI":"10.15252\/msb.202211361"},{"key":"e_1_2_10_24_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2023.08.003"},{"key":"e_1_2_10_25_1","unstructured":"Patterson W. R. J.Rossner R.Garuda M.Davis andG. 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