Causal effects of dietary antioxidants on epigenetic age: A two-sample Mendelian randomization study

Oxidative stress is one of the leading causes of aging and aging-related diseases. However, there is no conclusive evidence on whether dietary antioxidants can decelerate epigenetic age in human. A two-sample Mendelian randomization (MR) analysis was conducted to explore the causal associations between dietary antioxidants intake and epigenetic age. Summary-level data about 4 dietary antioxidants (vitamin A, vitamin C, vitamin E and carotene) and 4 epigenetic age measures (HannumAge, Intrinsic epigenetic age acceleration [IEAA], GrimAge and PhenoAge) were respectively got from FinnGen Project Database and a meta-analysis of 28 genome-wide association studies (GWAS) involving 34,710 European participants. Inverse variance weighted (IVW) was used as the main method to evaluate causal estimates complemented by other 4 methods (Weighted median, MR-Egger, Weighted mode and Simple mode). Genetically predicted dietary vitamin C was associated with decreased HannumAge (IVW: beta = -1.1988, P = .0014; weighted median: beta = -1.3342, P = .0112). IVW method found that dietary vitamin C was marginally associated with decreased GrimAge (beta = -0.768, P = .0504), other 4 methods did not find significant association between dietary vitamin C and GrimAge, but the effect direction was similar to that by IVW. There was no significant association of dietary vitamin C with IEAA and PhenoAge. MR analyses found no significant effects of vitamin A, vitamin E and carotene on 4 epigenetic age measures. In total, the study suggested that dietary vitamin C may potentially decrease epigenetic age measured by HannumAge. Further studies are needed to assess the effect of dietary antioxidants on aging and aging-related diseases, and explore related mechanisms.