The effect of polyphenols on DNA methylation-assessed biological age attenuation: the DIRECT PLUS randomized controlled trial
Abstract Background Epigenetic age is an estimator of biological age based on DNA methylation; its discrepancy from chronologic age warrants further investigation. We recently reported that greater polyphenol intake benefitted ectopic fats, brain function, and gut microbiota profile, corresponding w...
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BMC
2023-09-01
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| Series: | BMC Medicine |
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| Online Access: | https://doi.org/10.1186/s12916-023-03067-3 |
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| author | Anat Yaskolka Meir Maria Keller Anne Hoffmann Ehud Rinott Gal Tsaban Alon Kaplan Hila Zelicha Tobias Hagemann Uta Ceglarek Berend Isermann Ilan Shelef Matthias Blüher Michael Stumvoll Jun Li Sven-Bastian Haange Beatrice Engelmann Ulrike Rolle-Kampczyk Martin von Bergen Frank B. Hu Meir J. Stampfer Peter Kovacs Liming Liang Iris Shai |
| author_facet | Anat Yaskolka Meir Maria Keller Anne Hoffmann Ehud Rinott Gal Tsaban Alon Kaplan Hila Zelicha Tobias Hagemann Uta Ceglarek Berend Isermann Ilan Shelef Matthias Blüher Michael Stumvoll Jun Li Sven-Bastian Haange Beatrice Engelmann Ulrike Rolle-Kampczyk Martin von Bergen Frank B. Hu Meir J. Stampfer Peter Kovacs Liming Liang Iris Shai |
| author_sort | Anat Yaskolka Meir |
| collection | DOAJ |
| description | Abstract Background Epigenetic age is an estimator of biological age based on DNA methylation; its discrepancy from chronologic age warrants further investigation. We recently reported that greater polyphenol intake benefitted ectopic fats, brain function, and gut microbiota profile, corresponding with elevated urine polyphenols. The effect of polyphenol-rich dietary interventions on biological aging is yet to be determined. Methods We calculated different biological aging epigenetic clocks of different generations (Horvath2013, Hannum2013, Li2018, Horvath skin and blood2018, PhenoAge2018, PCGrimAge2022), their corresponding age and intrinsic age accelerations, and DunedinPACE, all based on DNA methylation (Illumina EPIC array; pre-specified secondary outcome) for 256 participants with abdominal obesity or dyslipidemia, before and after the 18-month DIRECT PLUS randomized controlled trial. Three interventions 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). Adherence to the Green-MED diet was assessed by questionnaire and urine polyphenols metabolomics (high-performance liquid chromatography quadrupole time of flight). Results Baseline chronological age (51.3 ± 10.6 years) was significantly correlated with all methylation age (mAge) clocks with correlations ranging from 0.83 to 0.95; p < 2.2e − 16 for all. While all interventions did not differ in terms of changes between mAge clocks, greater Green-Med diet adherence was associated with a lower 18-month relative change (i.e., greater mAge attenuation) in Li and Hannum mAge (beta = − 0.41, p = 0.004 and beta = − 0.38, p = 0.03, respectively; multivariate models). Greater Li mAge attenuation (multivariate models adjusted for age, sex, baseline mAge, and weight loss) was mostly affected by higher intake of Mankai (beta = − 1.8; p = 0.061) and green tea (beta = − 1.57; p = 0.0016) and corresponded with elevated urine polyphenols: hydroxytyrosol, tyrosol, and urolithin C (p < 0.05 for all) and urolithin A (p = 0.08), highly common in green plants. Overall, participants undergoing either MED-style diet had ~ 8.9 months favorable difference between the observed and expected Li mAge at the end of the intervention (p = 0.02). Conclusions 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. Trial registration ClinicalTrials.gov, NCT03020186. |
| first_indexed | 2024-03-09T15:08:01Z |
| format | Article |
| id | doaj.art-9cb62bb94b3e4e4983fd73d3f2b68a05 |
| institution | Directory Open Access Journal |
| issn | 1741-7015 |
| language | English |
| last_indexed | 2024-03-09T15:08:01Z |
| publishDate | 2023-09-01 |
| publisher | BMC |
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| series | BMC Medicine |
| spelling | doaj.art-9cb62bb94b3e4e4983fd73d3f2b68a052023-11-26T13:34:13ZengBMCBMC Medicine1741-70152023-09-0121111510.1186/s12916-023-03067-3The effect of polyphenols on DNA methylation-assessed biological age attenuation: the DIRECT PLUS randomized controlled trialAnat Yaskolka Meir0Maria Keller1Anne Hoffmann2Ehud Rinott3Gal Tsaban4Alon Kaplan5Hila Zelicha6Tobias Hagemann7Uta Ceglarek8Berend Isermann9Ilan Shelef10Matthias Blüher11Michael Stumvoll12Jun Li13Sven-Bastian Haange14Beatrice Engelmann15Ulrike Rolle-Kampczyk16Martin von Bergen17Frank B. Hu18Meir J. Stampfer19Peter Kovacs20Liming Liang21Iris Shai22The Health & Nutrition Innovative International Research Center, Faculty of Health Sciences, Ben-Gurion University of the NegevHelmholtz Institute for Metabolic, Obesity and Vascular Research (HI-MAG) of the Helmholtz Center Munich at the University of Leipzig and University Hospital LeipzigHelmholtz Institute for Metabolic, Obesity and Vascular Research (HI-MAG) of the Helmholtz Center Munich at the University of Leipzig and University Hospital LeipzigThe Health & Nutrition Innovative International Research Center, Faculty of Health Sciences, Ben-Gurion University of the NegevThe Health & Nutrition Innovative International Research Center, Faculty of Health Sciences, Ben-Gurion University of the NegevThe Health & Nutrition Innovative International Research Center, Faculty of Health Sciences, Ben-Gurion University of the NegevThe Health & Nutrition Innovative International Research Center, Faculty of Health Sciences, Ben-Gurion University of the NegevHelmholtz Institute for Metabolic, Obesity and Vascular Research (HI-MAG) of the Helmholtz Center Munich at the University of Leipzig and University Hospital LeipzigInstitute of Laboratory Medicine, Clinical Chemistry, and Molecular Diagnostics, University of Leipzig Medical CenterInstitute of Laboratory Medicine, Clinical Chemistry, and Molecular Diagnostics, University of Leipzig Medical CenterSoroka University Medical CenterHelmholtz Institute for Metabolic, Obesity and Vascular Research (HI-MAG) of the Helmholtz Center Munich at the University of Leipzig and University Hospital LeipzigHelmholtz Institute for Metabolic, Obesity and Vascular Research (HI-MAG) of the Helmholtz Center Munich at the University of Leipzig and University Hospital LeipzigDivision of Preventive Medicine, Department of Medicine, Brigham and Women’s Hospital and, Harvard Medical SchoolDepartment of Molecular Systems Biology, Helmholtz Centre for Environmental Research GmbHDepartment of Molecular Systems Biology, Helmholtz Centre for Environmental Research GmbHDepartment of Molecular Systems Biology, Helmholtz Centre for Environmental Research GmbHDepartment of Molecular Systems Biology, Helmholtz Centre for Environmental Research GmbHDepartment of Epidemiology, Harvard T.H. Chan School of Public HealthDepartment of Nutrition, Harvard T.H. Chan School of Public HealthMedical Department III – Endocrinology, Nephrology, Rheumatology, University of Leipzig Medical Center, University of LeipzigDepartment of Epidemiology, Harvard T.H. Chan School of Public HealthThe Health & Nutrition Innovative International Research Center, Faculty of Health Sciences, Ben-Gurion University of the NegevAbstract Background Epigenetic age is an estimator of biological age based on DNA methylation; its discrepancy from chronologic age warrants further investigation. We recently reported that greater polyphenol intake benefitted ectopic fats, brain function, and gut microbiota profile, corresponding with elevated urine polyphenols. The effect of polyphenol-rich dietary interventions on biological aging is yet to be determined. Methods We calculated different biological aging epigenetic clocks of different generations (Horvath2013, Hannum2013, Li2018, Horvath skin and blood2018, PhenoAge2018, PCGrimAge2022), their corresponding age and intrinsic age accelerations, and DunedinPACE, all based on DNA methylation (Illumina EPIC array; pre-specified secondary outcome) for 256 participants with abdominal obesity or dyslipidemia, before and after the 18-month DIRECT PLUS randomized controlled trial. Three interventions 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). Adherence to the Green-MED diet was assessed by questionnaire and urine polyphenols metabolomics (high-performance liquid chromatography quadrupole time of flight). Results Baseline chronological age (51.3 ± 10.6 years) was significantly correlated with all methylation age (mAge) clocks with correlations ranging from 0.83 to 0.95; p < 2.2e − 16 for all. While all interventions did not differ in terms of changes between mAge clocks, greater Green-Med diet adherence was associated with a lower 18-month relative change (i.e., greater mAge attenuation) in Li and Hannum mAge (beta = − 0.41, p = 0.004 and beta = − 0.38, p = 0.03, respectively; multivariate models). Greater Li mAge attenuation (multivariate models adjusted for age, sex, baseline mAge, and weight loss) was mostly affected by higher intake of Mankai (beta = − 1.8; p = 0.061) and green tea (beta = − 1.57; p = 0.0016) and corresponded with elevated urine polyphenols: hydroxytyrosol, tyrosol, and urolithin C (p < 0.05 for all) and urolithin A (p = 0.08), highly common in green plants. Overall, participants undergoing either MED-style diet had ~ 8.9 months favorable difference between the observed and expected Li mAge at the end of the intervention (p = 0.02). Conclusions 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. Trial registration ClinicalTrials.gov, NCT03020186.https://doi.org/10.1186/s12916-023-03067-3EpigeneticsWeight lossGreen-MED dietUrolithinsTyrosolMethylation age |
| spellingShingle | Anat Yaskolka Meir Maria Keller Anne Hoffmann Ehud Rinott Gal Tsaban Alon Kaplan Hila Zelicha Tobias Hagemann Uta Ceglarek Berend Isermann Ilan Shelef Matthias Blüher Michael Stumvoll Jun Li Sven-Bastian Haange Beatrice Engelmann Ulrike Rolle-Kampczyk Martin von Bergen Frank B. Hu Meir J. Stampfer Peter Kovacs Liming Liang Iris Shai The effect of polyphenols on DNA methylation-assessed biological age attenuation: the DIRECT PLUS randomized controlled trial BMC Medicine Epigenetics Weight loss Green-MED diet Urolithins Tyrosol Methylation age |
| title | The effect of polyphenols on DNA methylation-assessed biological age attenuation: the DIRECT PLUS randomized controlled trial |
| title_full | The effect of polyphenols on DNA methylation-assessed biological age attenuation: the DIRECT PLUS randomized controlled trial |
| title_fullStr | The effect of polyphenols on DNA methylation-assessed biological age attenuation: the DIRECT PLUS randomized controlled trial |
| title_full_unstemmed | The effect of polyphenols on DNA methylation-assessed biological age attenuation: the DIRECT PLUS randomized controlled trial |
| title_short | The effect of polyphenols on DNA methylation-assessed biological age attenuation: the DIRECT PLUS randomized controlled trial |
| title_sort | effect of polyphenols on dna methylation assessed biological age attenuation the direct plus randomized controlled trial |
| topic | Epigenetics Weight loss Green-MED diet Urolithins Tyrosol Methylation age |
| url | https://doi.org/10.1186/s12916-023-03067-3 |
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