Dietary pattern modifies associations between dietary factors and pace of epigenetic aging

Introduction: Epigenetic clocks, DNA methylation-based biomarkers indicating biological aging, are responsive to diet and lifestyle changes, but it remains unclear how specific dietary factors affect these indicators. Identifying dietary factors and overall dietary patterns that influence epigenetic clocks could help to inform dietary recommendations for healthy aging. Plant food-derived dietary factors, such as carotenoids, folate, and flavonoids, have been associated with a lower risk of cancer, but there has been little research on their associations with epigenetic aging, in particular, the pace of aging indicator DunedinPACE. We previously reported a slower pace of epigenetic aging, indicated by DunedinPACE, in females following a nutrient-dense, plant-rich ("Nutritarian") diet compared to those following a standard American diet (SAD). Here, in a secondary analysis, we aimed to determine whether selected food-derived dietary factors associated with reduced cancer risk and emphasized in the Nutritarian diet influenced DunedinPACE in this cohort. Methods: We investigated associations of carotenoids, flavonoids, and folate with DunedinPACE and other epigenetic aging indicators. Results: The Nutritarian group had significantly higher intakes of anthocyanidins, flavonols, flavan-3-ols, flavones, alpha-carotene, lutein and zeaxanthin, total folate, and food folate than the SAD group. With adjustment for diet group, body mass index (BMI), and menopausal status, intakes of anthocyanidins, flavonols, flavan-3-ols, lutein + zeaxanthin, total folate, and food folate were significantly associated with DunedinPACE. There were also significant dietary factor by group interactions. Higher intakes of these dietary factors were associated with lower DunedinPACE values in the Nutritarian group than in the SAD group. Conclusions: These results suggest that overall dietary patterns modify the relationships of individual food-derived nutrients and phytochemicals with DunedinPACE, and further support a Nutritarian diet as a strategy to slow epigenetic aging.