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

doi:10.1186/s13148-021-01218-y

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

Clin Epigenetics. 2021 Dec 17;13(1):224. doi: 10.1186/s13148-021-01218-y.

Authors

Jamaji C Nwanaji-Enwerem^#^{1

2}, Felicia Fei-Lei Chung^#^{3

4}, Lars Van der Laan⁵, Alexei Novoloaca³, Cyrille Cuenin³, Harriet Johansson^{6

7}, Bernardo Bonanni^{6

7}, Alan E Hubbard⁵, Martyn T Smith^#⁵, Sheri J Hartman^#^{8

9}, Andres Cardenas^#⁵, Dorothy D Sears^#^{7

9

10}, Zdenko Herceg^#³

Affiliations

¹ Department of Emergency Medicine, Gangarosa Department of Environmental Health, Emory University School of Medicine, Emory Rollins School of Public Health, 1518 Clifton Rd. NE, Atlanta, GA, 30322, USA. jnwanaj@emory.edu.
² Division of Environmental Health Sciences, School of Public Health and Center for Computational Biology, University of California, Berkeley, Berkeley, CA, USA. jnwanaj@emory.edu.
³ Epigenomics and Mechanisms Branch, International Agency for Research on Cancer, Lyon, France.
⁴ Department of Medical Sciences, School of Medical and Life Sciences, Sunway University, Petaling Jaya, Malaysia.
⁵ Division of Environmental Health Sciences, School of Public Health and Center for Computational Biology, University of California, Berkeley, Berkeley, CA, USA.
⁶ Division of Cancer Prevention and Genetics, IEO European Institute of Oncology IRCCS, Via Ripamonti, 435 - 20141, Milan, Italy.
⁷ College of Health Solutions, Arizona State University, Phoenix, AZ, USA.
⁸ Herbert Wertheim School of Public Health, University of California, San Diego, CA, USA.
⁹ Moores Cancer Center, University of California, San Diego, CA, USA.
¹⁰ Department Medicine, University of California, San Diego, CA, USA.

^# Contributed equally.

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://clinicaltrials.gov/ct2/show/NCT01302379.

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

Publication types

Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

MeSH terms

Aged
Aging / genetics*
Aging / physiology
Biomarkers, Tumor / analysis
Biomarkers, Tumor / genetics
Breast Neoplasms / diagnosis
Breast Neoplasms / physiopathology*
Female
Humans
Metformin / administration & dosage
Metformin / pharmacology*
Middle Aged
Overweight / epidemiology
Overweight / therapy*
Postmenopause
Survivors / statistics & numerical data
Weight Reduction Programs / methods
Weight Reduction Programs / standards
Weight Reduction Programs / statistics & numerical data

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

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