Research Paper|Volume 13, Issue 7|pp 9419—9432

Potential reversal of epigenetic age using a diet and lifestyle intervention: a pilot randomized clinical trial

Kara N. Fitzgerald¹, Romilly Hodges², Douglas Hanes³, Emily Stack⁴, David Cheishvili⁵, Moshe Szyf⁶, Janine Henkel⁷, Melissa W. Twedt⁷, Despina Giannopoulou⁷, Josette Herdell⁷, Sally Logan⁷, Ryan Bradley^7,⁸

¹Institute for Functional Medicine, Federal Way, WA 98003, USA
²American Nutrition Association, Hinsdale, IL 60521, USA
³Helfgott Research Institute, National University of Natural Medicine, Portland, OR 97201, USA
⁴Helfgott Research Institute, National University of Natural Medicine, Portland, OR 97201, USA
⁵HKG Epitherapeutics (Hong Kong), Department of Molecular Biology, Ariel University, Israel, Gerald Bronfman Department of Oncology, McGill University, Montreal, Quebec, Canada
⁶Department of Pharmacology and Therapeutics, McGill University, Montreal, QC H3G 1Y6, Canada
⁷Helfgott Research Institute, National University of Natural Medicine, Portland, OR 97201, USA
⁸Division of Preventive Medicine, University of California, San Diego, CA 92023, USA

Received: December 15, 2020Accepted: March 13, 2021Published: April 12, 2021

https://doi.org/10.18632/aging.202913

Copyright: © 2021 Fitzgerald et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Abstract

Manipulations to slow biological aging and extend healthspan are of interest given the societal and healthcare costs of our aging population. Herein we report on a randomized controlled clinical trial conducted among 43 healthy adult males between the ages of 50-72. The 8-week treatment program included diet, sleep, exercise and relaxation guidance, and supplemental probiotics and phytonutrients. The control group received no intervention. Genome-wide DNA methylation analysis was conducted on saliva samples using the Illumina Methylation Epic Array and DNAmAge was calculated using the online Horvath DNAmAge clock (2013). The diet and lifestyle treatment was associated with a 3.23 years decrease in DNAmAge compared with controls (p=0.018). DNAmAge of those in the treatment group decreased by an average 1.96 years by the end of the program compared to the same individuals at the beginning with a strong trend towards significance (p=0.066). Changes in blood biomarkers were significant for mean serum 5-methyltetrahydrofolate (+15%, p=0.004) and mean triglycerides (-25%, p=0.009). To our knowledge, this is the first randomized controlled study to suggest that specific diet and lifestyle interventions may reverse Horvath DNAmAge (2013) epigenetic aging in healthy adult males. Larger-scale and longer duration clinical trials are needed to confirm these findings, as well as investigation in other human populations.