Abstract A17: Physical activity and epigenetic age among normative aging study participants
Authors: Hibler Elizabeth A. , Zheng Yinan , Liu Lei , Zhang Wei , Penedo Frank J. , Phillips Siobhan M. , Conroy David E. , Schwartz Joel , Vokonas Pantel , Baccarelli Andrea , Dai Qi , Hou Lifang 
Published: May 2016

Abstract
Low levels of physical activity are associated with increased risk and mortality of common cancers including breast and colon, with strong evidence for increasing risk with age. Epigenetic age is a recently developed concept using DNA methylation measurements to describe biological age at the level of human tissues, cells, and organs. Epigenetic age represents deviation from expected DNA methylation patterns associated with chronological age (defined as Δ_age), and is suggested as a possible biological mechanism driving observed associations between physical activity and cancer risk. However, no studies have evaluated associations between physical activity level and Δ_age. The Normative Aging Study (NAS) is a cohort study of healthy aging conducted by the Veterans Affair Administration. Among NAS participants (n=656), we conducted multivariate linear regression to prospectively evaluate associations between physical activity (MET-hours per week) and Δ_age across two follow-up visits. The visits were on average 3.6 years apart, with a range of 2-8 years. Δ_age was estimated using Horvath’s DNA methylation online calculator and based upon DNA methylation patterns at the 71 cytosine-phosphate-guanine (CpGs) loci used in Hannum’s model. The calculator accounts for cell proportion of white blood cells. We adjusted models for chronological age, body mass index, education, smoking, alcohol consumption, and prevalent cancer status. Overall, we observed statistically significant associations between high physical activity levels and lower Δ_age, or younger epigenetic age. Among individuals reporting the highest level of physical activity (≥ 30 MET-hours per week), Δ_age was 1.44 (95% CI: 0.43 to 2.45) and 2.20 (95% CI: 1.04 to 3.36) years lower compared to those reporting low activity (&lt;12 MET-hours per week) at the first and second visit, respectively. Furthermore, compared to low physical activity, high activity at the first visit was associated with 2.46 (95% CI: 1.25 to 3.67) years lower Δ_age at the second visit, and 3.72 (95% CI: 1.08 to 6.36) months/calendar year lower Δ_age rate of change, or decelerated epigenetic aging over time. In summary, the results of the current study demonstrate that physical activity influences DNA methylation patterns at the CpG loci associated with epigenetic age. Future studies are necessary to characterize further the relationship between physical activity and epigenetic age, especially as a potential biological mechanism of action in carcinogenesis. However, epigenetic age represents a unique set of markers with the potential to identify high-risk populations and, in turn, develop interventions to mitigate risk of cancer.
Citation Format: Elizabeth A. Hibler, Yinan Zheng, Lei Liu, Wei Zhang, Frank J. Penedo, Siobhan M. Phillips, David E. Conroy, Joel Schwartz, Pantel Vokonas, Andrea Baccarelli, Qi Dai, Lifang Hou. Physical activity and epigenetic age among normative aging study participants. [abstract]. In: Proceedings of the AACR Special Conference: Developmental Biology and Cancer; Nov 30-Dec 3, 2015; Boston, MA. Philadelphia (PA): AACR; Mol Cancer Res 2016;14(4_Suppl):Abstract nr A17.