One-year Mediterranean diet promotes epigenetic rejuvenation with country- and sex-specific effects: a pilot study from the NU-AGE project

Noémie Gensous, Paolo Garagnani, Aurelia Santoro, Cristina Giuliani, Rita Ostan, Cristina Fabbri, Maddalena Milazzo, Davide Gentilini, Anna Maria di Blasio, Barbara Pietruszka, Dawid Madej, Agata Bialecka-Debek, Anna Brzozowska, Claudio Franceschi, Maria Giulia Bacalini, Noémie Gensous, Paolo Garagnani, Aurelia Santoro, Cristina Giuliani, Rita Ostan, Cristina Fabbri, Maddalena Milazzo, Davide Gentilini, Anna Maria di Blasio, Barbara Pietruszka, Dawid Madej, Agata Bialecka-Debek, Anna Brzozowska, Claudio Franceschi, Maria Giulia Bacalini

Abstract

Mediterranean diet has been proposed to promote healthy aging, but its effects on aging biomarkers have been poorly investigated. We evaluated the impact of a 1-year Mediterranean-like diet in a pilot study including 120 elderly healthy subjects from the NU-AGE study (60 Italians, 60 Poles) by measuring the changes in their epigenetic age, assessed by Horvath's clock. We observed a trend towards epigenetic rejuvenation of participants after nutritional intervention. The effect was statistically significant in the group of Polish females and in subjects who were epigenetically older at baseline. A genome-wide association study of epigenetic age changes after the intervention did not return significant (adjusted p value < 0.05) loci. However, we identified small-effect alleles (nominal p value < 10-4), mapping in genes enriched in pathways related to energy metabolism, regulation of cell cycle, and of immune functions. Together, these findings suggest that Mediterranean diet can promote epigenetic rejuvenation but with country-, sex-, and individual-specific effects, thus highlighting the need for a personalized approach to nutritional interventions.

Keywords: Biological age; DNA methylation; Epigenetic age acceleration; Epigenetic clock; Epigenetics; Mediterranean-like diet.

Conflict of interest statement

The authors declare that they have no competing interests.

Figures

Fig. 1
Fig. 1
Significant association between DNAm age and chronological age at T0 and T1. Scatter plots of chronological age (x-axis) versus DNAm age (y-axis) in the different groups (T0 = blue; T1 = red). Lines represent fitted linear regressions
Fig. 2
Fig. 2
A 1 year Mediterranean-like diet intervention promotes epigenetic rejuvenation in a country- and sex-specific manner. Boxplots of epigenetic AA measures at T0 and T1 (upper panel, AgeAccel; middle panel, IEAA; lower panel, EEAA) considering all the subjects, only males, and only females. Uncorrected p values and p values after correction for multiple testing are displayed.
Fig. 3
Fig. 3
Stronger impact of diet on epigenetic AA measures in subjects with higher epigenetic AA values at baseline. Scatter plots of epigenetic AA measures at T1 (x-axis) versus epigenetic AA measures difference between T1-T0 (y-axis). The three epigenetic AA measures (AgeAccel, IEAA, and EEEA) are reported respectively in the upper, middle, and lower panels. Males and females subjects are indicated with cyan and pink circles, respectively. The number of subjects in each quadrant is reported. Fisher’s exact test was applied to test if there was a difference of proportion of subjects in the 4 quadrants
Fig. 4
Fig. 4
Thirty-one SNPs associated with AgeAccel are common with IEAA. Venn diagram of SNPs associated with AgeAccel (blue), IEAA (yellow), and EEAA (green)

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