GeroScienceSep 10, 2026

Markers of Aging and DNA Changes in Women Receiving Chemotherapy for Early Breast Cancer

Longevity & Aging Weekly Brief ↗PubMed ↗DOI ↗OA ↗

Updated Sep 11, 2026

Abstract

T-cell p16 expression and five DNA methylation clocks were evaluated in 251 women with early breast cancer and 49 non-cancer controls.

Weak correlations were observed between T-cell p16 expression and DNA methylation clocks in both cancer patients and controls (r < 0.3).
Significantly higher levels of Hannum, GrimAge, and PhenoAge clocks were found in women with breast cancer compared to controls, even after adjusting for race, ethnicity, and BMI.
Following chemotherapy, T-cell p16 levels increased significantly within 3-6 months, while no significant changes were noted in the Horvath, PhenoAge, GrimAge, and mPoA clocks.
The Hannum age clock showed a modest increase (p = 0.02) post-chemotherapy.
T-cell p16 and DNA methylation clocks appear to reflect different aspects of biological aging and may respond differently to cancer and its treatment.

Simplified

Candidate biomarkers of biologic aging include p16^INK4a (p16) expression in peripheral blood T cells, a marker of cellular senescence, and whole-blood DNA methylation (DNAm) clocks, markers of epigenetic aging. Both have been associated with age-accelerating conditions, including cancer and chemotherapy, but their relationship has been inadequately studied. Biomarkers were evaluated in women with early breast cancer (n = 251) and non-cancer controls (n = 49). 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. Baseline correlations between p16 and DNAm clocks were weak in both cancer patients and controls (r < 0.3). 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 3-6 months, whereas Horvath, PhenoAge, GrimAge, and mPoA showed no significant change. Hannum age increased modestly (p = 0.02). T-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.

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Markers of Aging and DNA Changes in Women Receiving Chemotherapy for Early Breast Cancer

Abstract

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