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Objective: Epigenetic clocks have been associated with a variety of health outcomes and is significantly associated with pain outcomes that can be influenced by varying nutrient statuses, such as vitamin D. It is important to explore the factors that may influence vitamin Ds effects. Here, we sought to examine the mediating effects of obesity on the association between vitamin D and epigenetic aging among adults with and without chronic knee pain.

Methods: Self-reported pain, Waist-to-hip ratio, and blood samples to quantify vitamin D and epigenetic aging were collected.

Results: After controlling for covariates, there was no complete or indirect mediation of the vitamin D association with the epigenetic clock DNAGrimAgevia Waist-to-hip Ratio (WHR) of obesity in the pain group. However, upon adding sex into a moderatedmediation (sex moderating the relationship between vitamin D and WHR), there was a significant indirect effect of vitamin D status on AgeAccelGrim through WHR in females (ab=-0.0286; CI [-0.055,-0.009]), but not males (ab=-0.0067; CI [-0.0451, 0.0216]) in the pain group.

Conclusions: While novel, the data from this study highlight the important role that vitamin D plays within the genomic environment, as well as how the contribution of obesity in a sex-dependent manner may potentially influence this relationship.