Preliminary longitudinal epigenetic clock analyses of patients with mild cognitive impairment through nutritional
Kiriko Minami1, Toshiyuki Shirai1, Satoshi Okazaki1
1Department of Psychiatry, Kobe University Graduate School of Medicine, Kobe, Japan.
Abstract:
BackgroundMild 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.ObjectiveWe 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.MethodsWe 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.ResultsIn 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.ConclusionsWe 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.
Insights
Interventions with vitamin D and/or omega-3 fatty acids may slow biological aging in individuals with mild cognitive impairment (MCI). This study observed decelerated epigenetic clocks, suggesting a potential protective effect against progression to dementia.
Area of Science:
- Gerontology
- Neuroscience
- Epigenetics
Background:
- Mild cognitive impairment (MCI) represents a transitional stage between normal aging and dementia.
- A significant proportion of MCI patients progress to Alzheimer's disease annually.
- Epigenetic clock analysis is emerging as a key tool in aging research and dementia prevention.
Purpose of the Study:
- To evaluate the impact of vitamin D and/or marine omega-3 fatty acid supplementation on epigenetic aging in MCI patients.
- To conduct longitudinal epigenetic clock analysis to assess biological changes over a two-year intervention period.
Main Methods:
- Utilized public DNA methylation datasets from the Gene Expression Omnibus (GEO) database.
- Analyzed longitudinal data from 25 MCI patients and 20 controls over two years.
- Employed Wilcoxon signed-rank tests and three regression models for comparative and analytical assessments.
Main Results:
- PhenoAge and GrimAge epigenetic clocks showed significant deceleration in MCI patients post-intervention.
- Regression analyses indicated nominal deceleration for these epigenetic clocks.
- Significant pre- and post-intervention differences were noted in natural killer cell populations.
Conclusions:
- Supplementation with vitamin D and/or omega-3 fatty acids demonstrated a deceleration effect on specific epigenetic clocks in MCI patients.
- These findings highlight the potential of interventions to modify biological aging processes in MCI.
- Further research with larger cohorts and diverse interventions (e.g., occupational therapy, pharmacotherapy) is recommended to validate and expand upon these results.
