An epigenetic aging analysis of randomized metformin and weight loss interventions in overweight postmenopausal breast cancer survivors

Jamaji C Nwanaji-Enwerem, Felicia Fei-Lei Chung, Lars Van der Laan, Alexei Novoloaca, Cyrille Cuenin, Harriet Johansson, Bernardo Bonanni, Alan E Hubbard, Martyn T Smith, Sheri J Hartman, Andres Cardenas, Dorothy D Sears, Zdenko Herceg, Jamaji C Nwanaji-Enwerem, Felicia Fei-Lei Chung, Lars Van der Laan, Alexei Novoloaca, Cyrille Cuenin, Harriet Johansson, Bernardo Bonanni, Alan E Hubbard, Martyn T Smith, Sheri J Hartman, Andres Cardenas, Dorothy D Sears, Zdenko Herceg

Abstract

Metformin and weight loss relationships with epigenetic age measures-biological aging biomarkers-remain understudied. We performed a post-hoc analysis of a randomized controlled trial among overweight/obese breast cancer survivors (N = 192) assigned to metformin, placebo, weight loss with metformin, or weight loss with placebo interventions for 6 months. Epigenetic age was correlated with chronological age (r = 0.20-0.86; P < 0.005). However, no significant epigenetic aging associations were observed by intervention arms. Consistent with published reports in non-cancer patients, 6 months of metformin therapy may be inadequate to observe expected epigenetic age deceleration. Longer duration studies are needed to better characterize these relationships.Trial Registration: Registry Name: ClincialTrials.Gov.Registration Number: NCT01302379.Date of Registration: February 2011.URL: https://ichgcp.net/clinical-trials-registry/NCT01302379.

Keywords: Biomarkers; DNA methylation age; GrimAge; PhenoAge; RCT.

Conflict of interest statement

The authors declare that they have no competing interests.

© 2021. The Author(s).

Figures

Fig. 1
Fig. 1
Epigenetic Age and Chronological Age Pearson Correlations. Figure presents the baseline chronological age and epigenetic age correlation coefficients for the study sample (N = 192) for DNAmAge Hannum (A), DNAmAge Horvath (B), DNAmAge SkinBloodClock (C), DNAm PhenoAge (D), DNAm GrimAge (E), DNAm TL (F), EpiTOC (G), EpiTOC2 (H), and MiAge (I)

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