The effect of polyphenols on DNA methylation-assessed biological age attenuation


Accelerated biological aging, apart from chronological age, is associated with the pathogenesis of chronic morbidities, such as cardiovascular, musculoskeletal, renal, neurodegenerative, and neoplastic diseases. Biological aging can be assessed using DNA methylation, known as methylation age, which is highly correlated with chronological age. A healthy lifestyle combining a balanced diet including dietary supplements and vitamins, good sleep, and stress management beneficially alters the methylation age signatures.
 

The Mediterranean (MED) diet might increase lifespan and improve aging due to its unique combination of fatty acids, antioxidants, vitamins, and phytochemicals. Polyphenols, metabolites with antioxidant properties that are enriched in the MED diet, may affect epigenetic modifications via different mechanisms, including inhibition of DNA methyl transferase 1 (DNMT1), a central enzyme catalyzing DNA methylation.
 

Together with an assessment of Mankai (Wolffia globosa strain) plant polyphenols, which revealed 200 different phenolic compounds, this study showed that some of these compounds and their derivatives were present in the urine following high-polyphenol intervention. Furthermore, some urine polyphenols as urolithin A were differentially elevated in the groups that consumed more dietary polyphenols. They recently reported that greater polyphenol intake benefitted ectopic fats, brain function, and gut microbiota profile, corresponding with elevated urine polyphenols.
 

Total 256 participants with abdominal obesity or dyslipidemia were assigned: healthy dietary guidelines, a Mediterranean (MED) diet, and a polyphenol‑rich, low‑red/processed meat Green‑MED diet. Both MED groups consumed 28 g walnuts/day (+ 440 mg/day polyphenols). The Green‑MED group consumed green tea (3–4 cups/day) and Mankai (Wolffia globosa strain) 500‑ml green shake (+ 800 mg/day polyphenols).

This study showed that MED and green‑MED diets with increased polyphenols intake, such as green tea and Mankai, are inversely associated with biological aging. To the best of our knowledge, this is the first clinical trial to indicate a potential link between polyphenol intake, urine polyphenols, and biological aging.
 

Reference:
Yaskolka Meir A, Keller M, Hoffmann A, et al. The effect of polyphenols on DNA methylation-assessed biological age attenuation: the DIRECT PLUS randomized controlled trial. BMC Med. 2023; 21(1): 364.

12-19-2025 updated.

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