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Both have been associated with age-accelerating conditions, including cancer and chemotherapy, but their relationship has been inadequately studied.\u00a0Biomarkers were evaluated in women with early breast cancer (\n                    <jats:italic>n<\/jats:italic>\n                    \u2009=\u2009251) and non-cancer controls (\n                    <jats:italic>n<\/jats:italic>\n                    \u2009=\u200949). T-cell p16 expression and five DNAm clocks (Horvath, Hannum, PhenoAge, GrimAge, and Dunedin Pace of Aging [mPoA]) were measured. Baseline associations were assessed using Pearson correlations, and biomarker levels were compared between groups using age-adjusted linear regression models controlling for race, ethnicity, and BMI. In a subset of patients receiving chemotherapy, pre- and post-treatment changes were analyzed.\u00a0Baseline correlations between p16 and DNAm clocks were weak in both cancer patients and controls (\n                    <jats:italic>r<\/jats:italic>\n                    \u2009&lt;\u20090.3). No significant associations were observed between p16 and Horvath or mPoA clocks. In contrast, Hannum, GrimAge, and PhenoAge were significantly higher in women with breast cancer, and these differences remained after adjustment for covariates. Following chemotherapy, p16 increased significantly within 3\u20136\u00a0months, whereas Horvath, PhenoAge, GrimAge, and mPoA showed no significant change. Hannum age increased modestly (\n                    <jats:italic>p<\/jats:italic>\n                    \u2009=\u20090.02).\u00a0T-cell p16 and whole-blood DNAm clocks were only weakly correlated and demonstrated different responses to chemotherapy. These findings suggest that cellular senescence and epigenetic clocks reflect distinct aspects of biologic aging and may respond differently to cancer and its treatment.\n                  <\/jats:p>","DOI":"10.1007\/s11357-026-02521-3","type":"journal-article","created":{"date-parts":[[2026,9,10]],"date-time":"2026-09-10T06:40:35Z","timestamp":1789022435000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["p16INK4a and DNA methylation clocks in women treated with chemotherapy for early breast cancer"],"prefix":"10.1007","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2862-9970","authenticated-orcid":false,"given":"Hyman B.","family":"Muss","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Canlan","family":"Sun","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuan Chun","family":"Ding","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jingran","family":"Ji","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas A.","family":"White","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kirsten","family":"Nyrop","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nathan K.","family":"LeBrasseur","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Susan L.","family":"Neuhausen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Natalia","family":"Mitin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8379-391X","authenticated-orcid":false,"given":"Mina S.","family":"Sedrak","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,9,10]]},"reference":[{"key":"2521_CR1","first-page":"45","volume":"39","author":"J Campisi","year":"2014","unstructured":"Campisi J, Robert L. 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NM, SLS, and AK are equity holders in the company and inventors on intellectual property applications. Mayo Clinic and NKL have relevant technology licensed to a commercial entity. This research has been reviewed by the Mayo Clinic Conflict\u00a0of Interest Review Board and is being conducted in compliance with Mayo Clinic Conflict of Interest policies. All other authors declare no competing interests.","order":1,"name":"Ethics","label":"Competing interests","group":{"name":"EthicsHeading","label":"Declarations"}}]}}