Evaluating the connection between diet quality, EpiNutrient intake and epigenetic age: an observational study

Abstract

Background: DNA methylation (DNAm) has unique properties which makes it a potential biomarker for lifestyle-related exposures. Epigenetic clocks, particularly DNAm-based biological age predictors [epigenetic age (EA)], represent an exciting new area of clinical research and deviations of EA from chronological age [epigenetic age acceleration (EAA)] have been linked to overall health, age-related diseases, and environmental exposures.

Objectives: This observational study investigates the relationships between biological aging and various dietary factors within the LifeLines-DEEP Cohort. These factors include diet quality, processed food consumption, dietary glycemic load, and intake of vitamins involved in maintaining the epigenetic homeostasis (vitamins B-9, B-12, B-6, B-2, and C).

Methods: Dietary records collected using food-frequency questionnaires were used to estimate diet quality [LifeLines Diet Score (LLDS)], measure the intake of unprocessed/ultraprocessed food according to the NOVA food classification system, and the adequacy of the dietary intake of vitamins B-9, B-12, B-2, B-6, and C. EA using Horvath, Hannum, Levine, and Horvath2 epigenetic clock models and DNAm-predicted telomere length (DNAm-TL) were calculated from DNAm data in 760 subjects. Associations between dietary factors and EAA were tested, adjusting for sex, energy intake, and body composition.

Results: LLDS was associated with EAA (EAA_Horvath: β: -0.148; P = 1 × 10^-4; EAA_Hannum: β: -0.148; P = 9 × 10^-5; EAA_Levine: β: -0.174; P = 1 × 10^-5; and EAA_Horvath2: β: -0.176; P = 4 × 10^-6) and DNAm-TL (β: 0.116; P = 0.003). Particularly, EAA was associated with dietary glycemic load (EAA_Horvath: β: 0.476; P = 9 × 10^-10; EAA_Hannum: β: 0.565; P = 1 × 10^-13; EAA_Levine: β: 0.469; P = 5 × 10^-9; EAA_Horvath2: β: 0.569; P = 1 × 10^-13; and DNAmTL adjusted for age: β: -0.340; P = 2 × 10^-5) and different measures of food processing (NOVA classes 1 and 4). Positive EAA was also associated with inadequate intake of vitamin B-12 (EAA_Horvath: β: -0.167; P = 0.002; EAA_Hannum: β: -0.144; P = 0.007; and EAA_Horvath2: β: -0.126; P = 0.019) and C (EAA_Hannum: β: -0.136; P = 0.010 and EAA_Horvath2: β: -0.151; P = 0.005).

Conclusions: Our findings corroborate the hypothesis that nutrition plays a pivotal role in influencing epigenetic homeostasis, especially DNAm, thereby contributing to individual health trajectories and the pace of aging.

Keywords: 1-carbon metabolism; DNA methylation; aging; diet; epigenetic clocks; nutrigenomics; nutritional epigenomics.