“An Epigenetic Aging Analysis of Randomized Metformin and Weight Loss Interventions in Overweight Postmenopausal Breast Cancer Survivors”, 2021-12-17 (; similar):
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 (NCT01302379) 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 [Hannum, Horvath, SkinBloodClock, PhenoAge, DNAm TL, MiAge] was correlated with chronological age (r = 0.20–0.86; p < 0.005). However, no statistically-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.
[Keywords: RCT, DNA methylation age, biomarkers, GrimAge, PhenoAge]
…In unadjusted intent-to-treat models, when compared to placebo, no treatment arm demonstrated any statistically-significant differences or notable trends for any EA marker (Table 1). The results remained null even when intent-to-treat models included adjustments for leukocyte composition and number of days from randomization to the end of the study. Unadjusted and adjusted sensitivity analyses that focused on examining differences between high intervention adherence women and those in the placebo group also did not demonstrate any notable trends for any EA marker. Although weight loss—compared to placebo—was associated with EA in high adherence models, the association was in the opposite direction as expected and would not persist after multiple testing adjustment.