Preliminary longitudinal epigenetic clock analyses of patients with mild cognitive impairment through nutritional intervention

Background Mild cognitive impairment (MCI) is an intermediate stage between normal aging and dementia. Not a small number of patients with MCI progress to Alzheimer's disease within 1 year. Epigenetic changes in DNA methylation, such as those observed in the epigenetic clock, are receiving increasing attention in the field of aging research. It is crucial to demonstrate the effectiveness of interventions for patients with MCI from a biological perspective to promote the prevention of dementia. Objective We conducted epigenetic clock analysis, mainly longitudinal evaluation, on patients with MCI who received intervention with vitamin D and/or marine omega-3 fatty acid supplements. Methods We conducted epigenetic clock analyses with public DNA methylation datasets from the Gene Expression Omnibus database. This dataset contains two timepoints’ longitudinal DNA methylation data of 25 patients with MCI and 20 controls. They received two-year intervention with vitamin D and/or marine omega-3 fatty acid supplements. We conducted comparative analyses with Wilcoxon signed-rank test, and regression analyses of three models. Results In patients with MCI, PhenoAge and GrimAge significantly decelerated after the intervention in comparative analyses. These clocks nominally significantly decelerated also in most of regression analyses. Moreover, natural killer cells showed significant differences before and after the intervention. Conclusions We found deceleration of some epigenetic clocks in patients with MCI with interventions. We believe that it is crucial to conduct additional epigenetic clock analyses in cohorts with larger sample sizes or in cohorts with interventions such as occupational therapy and pharmacotherapy are actively conducted.