Authors :
Christa Habela, MD, PhD – Johns Hopkins School of Medicine
Anna Patnaik, MD – Johns Hopkins School of Medicine
Ann Isphording, BA 2026 – Johns Hopkins University
Presenting Author: Emily L. Johnson, MD, MPH – Johns Hopkins University
Rationale:
DNA methylation is an epigenetic mechanism by which cells modify gene expression without altering DNA sequence, and is increasingly recognized as an important contributor to chronic diseases. Epigenetic age is a validated calculation of an individual’s “biological age,” developed from DNA methylation in healthy individuals, which is influenced by environmental exposures and disease. Epigenetic age accurately predicts other aging markers and mortality, and advanced epigenetic age is associated with worse outcomes. We sought to determine the relationship between epigenetic age and chronological age in individuals with epilepsy.
Methods:
We collected baseline (admission) blood samples from people with epilepsy in the adult Epilepsy Monitoring Unit. We extracted DNA, and used the Illumina Infinium MethylationEPIC v2.0 array to perform bisulfite conversion and quantify methylation at 937,055 CpG sites. We then used R Studio to calculate epigenetic age according to the Horvath method, which uses methylation profiles at 353 CpG sites to calculate an individual’s biological age.
Results:
We analyzed samples from 18 adult patients with epilepsy obtained at EMU admission. This included 10 women and 8 men, 3 Black and 15 white individuals, and 4 with generalized epilepsy and 14 with focal epilepsy (Table). The median chronological age at admission was 31.3 (range 18.9-68 years), and the median seizure frequency was 2 seizures per month (range 0-13).
The epigenetic age was older than the chronological age in 14 of 18 individuals with epilepsy (Figure A). Mean age difference was 4.2 years older (standard deviation 5.5 years). Higher baseline seizure frequency was associated with increased age difference, with average excess epigenetic age 6.4 years in those with at least one seizure per month, and -0.1 years in those with < 1 seizure per month (p=0.01). Each additional average monthly seizure was associated with 0.25 years of excess epigenetic age (Figure B). There was no difference in epigenetic aging in those with focal versus those with generalized epilepsy in this sample (p=0.56). There were no interactions between age difference and seizure frequency and sex or race.
Conclusions:
Prior work has demonstrated that DNA methylation is altered by seizures and chronic epilepsy. We found that these methylation changes substantially affect the CpG regions that are critical markers for biological aging, with a measurable effect on an individual’s epigenetic age. DNA methylation may be one mechanism by which epilepsy puts individuals at risk for comorbidities and early mortality. These findings have potential therapeutic implications, as various methylation-modifying treatments are under study. For example, the ketogenic diet (an effective antiseizure treatment for some individuals with epilepsy) reduces abnormal methylation patterns in animal models, and restoration of typical methylation patterns through dietary modification is a promising treatment in this area. Future work will examine the effect of different seizure types and age of epilepsy onset on DNA methylation profiles.
Funding: Johns Hopkins Core Coins