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

Kara N Fitzgerald, Romilly Hodges, Douglas Hanes, Emily Stack, David Cheishvili, Moshe Szyf, Janine Henkel, Melissa W Twedt, Despina Giannopoulou, Josette Herdell, Sally Logan, Ryan Bradley, Kara N Fitzgerald, Romilly Hodges, Douglas Hanes, Emily Stack, David Cheishvili, Moshe Szyf, Janine Henkel, Melissa W Twedt, Despina Giannopoulou, Josette Herdell, Sally Logan, Ryan Bradley

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.

Keywords: DNA methylation; aging; biological clock; epigenetic; lifestyle.

Conflict of interest statement

CONFLICTS OF INTEREST: KF and RH declare that they use the intervention described here in clinical practice, are named in a related patent application, and receive earnings from educational products associated with its use. Notably, KF and RH were not involved in the day-to-day conduct of the trial, collection of samples, or data analysis.

Figures

Figure 1
Figure 1
CONSORT 2010 flow diagram.
Figure 2
Figure 2
Comparison of DNAmAge change between treatment and control groups. Each dot is a subject, and the vertical axis represents difference in DNAmAge from the beginning to the end of the eight-week term. Participants scored an average 1.96 years younger, controls an average 1.27 years older. The age reduction of the treatment group strongly trended towards significance (p=0.066), while the age increase of the control group itself was not significant (p=0.153). The difference between control and treatment groups was significant at the level p=0.018 (unpaired two-tailed t-test). Long red and blue lines represent group averages (mean).
Figure 3
Figure 3
Intervention group age change. Participants scored an average of 1.96 years younger than baseline (p=0.066). Of 18 participants included in the final analysis, 8 scored age reduction, 9 were unchanged, and 1 increased in methylation age.

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