Epigenetic age acceleration in adolescence: cross-sectional associations with dietary intake and prospective associations with cardiometabolic risk indicators in a Mexico City cohort.

BACKGROUND AND AIMS: To examine the cross-sectional relationship between dietary intake and epigenetic age acceleration, as well as the prospective relationship between epigenetic age acceleration and cardiometabolic parameters measured two years later.

METHODS AND

RESULTS

In 526 adolescents aged 7-18 years (average age 14.50) residing in Mexico City, dietary intake was assessed using a semi-quantitative food frequency questionnaire. Adherence to three dietary patterns was derived from principal component analysis. Blood leukocyte DNA methylation was measured with the Illumina Infinium MethylationEPIC BeadChip, from which epigenetic age acceleration was calculated for six epigenetic clocks: Horvath, Skin-Blood, PhenoAge, GrimAge, Pediatric-Buccal-Epigenetic (PedBE), and Wu. Nine cardiometabolic parameters were assessed two years after assessment of diet and epigenetic age acceleration. Linear regression models for sex-stratified associations were examined. Among males, the Meat & Starchy foods pattern was positively associated with Wu epigenetic age acceleration, showing a 0.096-year increase, while folate intake in females was associated with a 0.004-year decelerated GrimAge. Prospective analysis showed positive associations between epigenetic age acceleration and fat distribution and insulin resistance, particularly in males. In females, only GrimAge acceleration was associated in the expected manner with increased waist circumference (β = 0.62 cm), BMI (β = 0.25 kg/m2), fasting insulin (β = 0.86 μIU/mL), and insulin resistance (β = 0.21). Skin-Blood acceleration was associated with decreased HDL in males, and PedBE acceleration was associated with triglycerides in both sexes, though in opposing directions.

CONCLUSION

Adolescent diet was not strongly associated with baseline epigenetic age acceleration. However, epigenetic age acceleration was associated prospectively with fat distribution and insulin resistance.