DISCOVERY: Diet and Lifestyle Study Shows Possible Reversal in Epigenetic Age in a Pilot Clinical Trial

Diet and Lifestyle Study Shows Possible Reversal in Epigenetic Age in a Pilot Clinical Trial

A new study shows just how lifestyle changes and diet can slow the biological aging process and extend health span by three years. According to this small pilot randomized clinical trial, within an 8-week treatment program including diet, sleep, exercise and relaxation guidance, as well as supplemental probiotics and phytonutrients, participants showed a reversal in epigentic age. The scientists estimate that this reversed the biological clock by 3.2 years, as compared those who did not participate in the program.

This was independently piloted by the Helfgott Research Institute in collaboration with the Yale University Center for Genome Analysis laboratory. The results were independently examined at McGill University and the National University for Natural Medicine, Portland, Oregon and published in the journal Aging.

The randomized controlled clinical trial included 43 healthy adult males between the ages of 50-72. The study measured the Horvath DNAmAge clock, which predicts all-cause mortality and multiple morbidities better than chronological age. Methylation clocks (including DNAmAge) are based on systematic methylation changes with age. DNAmAge clock specifically demonstrates about 60% of DNA CpG sites lose methylation with age and 40% gain methylation.

“The combined intervention program was designed to target a specific biological mechanism called DNA methylation, and in particular the DNA methylation patterns that have been identified as highly predictive of biological age. We suspect that this focus was the reason for its remarkable impact. These early results appear to be consistent with, and greatly extend, the very few existing studies that have so far examined the potential for biological age reversal. And it is unique in its use of a safe, non-pharmaceutical dietary and lifestyle program, control group, and the extent of the age reduction. We are currently enrolling participants for a larger study which we expect will corroborate these findings,” Kara Fitzgerald ND IFMCP, the study’s lead author stated in a Newswire press statement.

Diet and Lifestyle Interventions for a Reversal in Epigentic Age

  • Foods were plant-centered, with limited nutrient-dense animal proteins (e.g. liver, egg). See the list here under materials and methods.
  • The diet restricted carbohydrates and included mild intermittent fasting, both designed to lower glycemic cycling.
  • The diet also included a high intake of nutrients that are substrates or cofactors in methylation biosynthetic pathways (e.g. containing folate, betaine), ten-eleven translocation (TET) demethylase cofactors and modulators (e.g. alpha ketoglutarate, vitamin C and vitamin A) and polyphenolic modulators of DNA methyl transferases (DNMT) (e.g. curcumin, epigallocatechin gallate (EGCG), rosmarinic acid, quercetin, luteolin). See the video below for brands.
  • The diet was also supplemented daily with a fruit and vegetable powder, also rich in polyphenolic modulators of DNMT activity (PhytoGanix®, see video below for more).
  • It included a probiotic providing 40 million CFU of Lactobacillus plantarum 299v. L. plantarum has been shown to be a folate producer in the presence of para aminobenzoic acid (PABA); it also has been demonstrated to alter gene expression (UltraFlora® Intensive Care. See the video below for more on brands.
  • The study also required a minimum of 30 minutes of exercise per day, at least 5 days per week at an intensity of 60-80 percent of maximum perceived exertion.
  • Participants used twice-daily breathing exercises to elicit the Relaxation Response for stress reduction (per the book, Steps to Elicit the Relaxation Response developed by Herbert Benson MD). A study cited in the report shows that 60 days of relaxation practice designed to elicit the Relaxation Response, 20 minutes twice per day, may significantly reduce DNAmAge, as measured by the Zbieć-Piekarska clock in a group of healthy participants (though not in their ‘patient’ group).
  • Regular coaching sessions, delivered weekly during the first four weeks, and then at least every other week thereafter were conducted to ensure program compliance.

Reversal of Epigenetic Age in Control and Treatment Group

Diet and Lifestyle Study Shows Possible Reversal in Epigenetic Age in a Pilot Clinical Trial
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).

Of note is that for both treatment and control groups, “there was no net increase or decrease in methylation of the 353 sites that compose the Horvath clock.” The researchers believe this suggests that the intervention did not lead to an overall increase in methylation of the Horvath clock sites. Instead it prompted a repositioning of clock’s CpG methylation patterns, which are consistent with a younger biological age

  • Also, for the blood markers, the most significant change was a 25% decrease in mean triglycerides from 112 to 89 mg/dL (p=0.009) over the eight-week study period. The folate rich diet also resulted in a rise of mean serum 5-methyltetrahydrofolate (5-MTHF) of 15% from 78 to 88 nmol/L (p=0.004).
  • No other blood markers measured changed significantly compared to controls, including glucose, hemoglobin A1C, total cholesterol, HDL cholesterol, LDL cholesterol, methionine, s-adenosylmethionine (SAM), s-adenosylhomocysteine (SAH) the ratio SAM:SAH and homocysteine, However, within the participants in the treatment group, they showed significant decrease in total cholesterol (-22.8 mg/dL, p=0.004) and LDL cholesterol (-16.8 mg/dL, p=0.01).
  • When measuring the PROMIS markers of emotional health, there were no statistically significant changes between treatment and control groups. They did see a slight trends toward reduced anxiety scores in the treatment group, though not statistically significant.

“What is extremely exciting, is that food and lifestyle practices, including specific nutrients and food compounds known to selectively alter DNA methylation, are able to have an impact on those DNA methylation patterns we know predict aging and age-related disease. I believe that this, together with new possibilities for us all to measure and track our DNA methylation age, will provide significant new opportunities for both scientists and consumers,” said Dr. Fitzgerald.

Conclusion/ ‘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 the researchers 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.”

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For more on DNA Methylation from Dr. Fitzgerald.


Source: Fitzgerald KN, Hodges R, Hanes D, Stack E, Cheishvili D, Szyf M, Henkel J, Twedt MW, Giannopoulou D, Herdell J, Logan S, Bradley R. Potential reversal of epigenetic age using a diet and lifestyle intervention: a pilot randomized clinical trial. Aging (Albany NY). 2021; 13:9419-9432. doi.org/10.18632/aging.202913