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Eat Your Greens – More Science Behind Polyphenols, DNA methylation & Epigenetic Aging

A table spread with vegetables and various food.
 

By Stuart P. Atkinson, Ph.D.

January 15, 2025

Introduction: The Links Between Healthy Living and DNA Methylation-based Epigenetic Aging

Researchers guided by Peter Kovacs, Liming Liang, and Iris Shai have begun to reveal the epigenetic impact of healthy living; a previous study reported the positive impact of weight loss and improved liver fat status on DNA methylation-based epigenetic aging in abdominally obese participants in a randomized controlled trial (Yaskolka Meir et al. 2021). The trial participants underwent an 18-month intervention that involved following a low-fat diet or a Mediterranean/low-carbohydrate diet. Polyphenols - metabolites with antioxidant properties – are enriched in the Mediterranean diet and have been shown to induce chromatin remodeling (Russo et al.); however, specific links between the intake of polyphenolic species and DNA methylation-based epigenetic aging remained largely unexplored.

This data gap prompted the researchers to next explore the potentially beneficial epigenetic effects of a “green-Mediterranean” diet - richer in polyphenol-rich green plant products and lower in meat - through their 18-month DIRECT-PLUS trial (dietary intervention randomized controlled trial polyphenols-unprocessed; NCT03020186). Their findings now forge a positive link between dietary polyphenol intake as part of a green-Mediterranean diet and DNA-methylation-based epigenetic aging.

Active Motif DNA Methylation

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Increased Dietary Polyphenols Slow the Epigenetic Aging Process

As reported in Clinical Epigenetics (Yaskolka Meir and Keller et al.), the team employed a variety of DNA methylation-based epigenetic clocks to measure the impact of three interventions on the DNA methylation-based epigenetic aging of 256 participants with abdominal obesity or dyslipidemia (a metabolic disorder characterized by abnormally high/low amounts of lipids/lipoproteins in the blood). The three interventions involved i) following basic health-promoting guidelines for achieving a healthy diet, ii) eating a Mediterranean diet, and iii) eating a polyphenol-rich, low-red/processed meat green-Mediterranean diet, with adherence to these diets assessed by a questionnaire and polyphenol metabolomic analysis. The study evaluated DNA methylation in blood samples using Illumina HumanMethylation850 Bead Chips (Hoffman et al.) and polyphenol levels in urine samples via high-performance liquid chromatography quadrupole time of flight analysis.

While the authors did not encounter any reductions in DNA methylation-base epigenetic aging in relation to adherence to these interventions, they did discover that greater adherence to the green-Mediterranean diet richer in polyphenols prompted the more significant slowing of DNA methylation-based epigenetic aging when measured by the Li (Li et al.) and Hannum (Hannum et al.) epigenetic clocks. Greater intake of polyphenols from sources such as green plant products induced more significant DNA methylation-based epigenetic age attenuation according to the Li epigenetic clock, which corresponded to increased levels of polyphenols such as hydroxytyrosol, tyrosol, urolithin C, and urolithin A in the urine. Additionally, the dietary changes evaluated in this clinical trial prompted beneficial effects on multiple health conditions (e.g., fatty liver, age-related brain atrophy, and cardiovascular risk), which may contribute to healthy aging, and supported weight loss in each intervention group.

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Polyphenols: A Critical Means of Slowing Epigenetic Aging?

The authors state that their clinical trial is the first to provide evidence that dietary polyphenol intake as part of a green-Mediterranean diet can positively influence DNA-methylation-based epigenetic aging; however, they note the need to confirm their findings through complementary studies.

For more on how a polyphenol-rich Mediterranean diet can positively impact DNA methylation-based epigenetic aging, see Clinical Epigenetics, September 2023.

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About the author

Stuart P. Atkinson

Stuart P. Atkinson, Ph.D.

Stuart was born and grew up in the idyllic town of Lanark (Scotland). He later studied biochemistry at the University of Strathclyde in Glasgow (Scotland) before gaining his Ph.D. in medical oncology; his thesis described the epigenetic regulation of the telomerase gene promoters in cancer cells. Following Post-doctoral stays in Newcastle (England) and Valencia (Spain) where his varied research aims included the exploration of epigenetics in embryonic and induced pluripotent stem cells, Stuart moved into project management and scientific writing/editing where his current interests include polymer chemistry, cancer research, regenerative medicine, and epigenetics. While not glued to his laptop, Stuart enjoys exploring the Spanish mountains and coastlines (and everywhere in between) and the food and drink that it provides!

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