Evidence map›Paper›PMID 42632233›Full record

ArticleEBioMedicine2026

Epigenetic ageing is accelerated in drug-resistant epilepsy and dynamically modulated during ketogenic diet therapy.

Kristina Gervin, Magnhild Kverneland, Karl Otto Nakken, Knut Rudi, Per Ole Iversen, Kaja Kristine Selmer

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Article in EBioMedicine, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

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4 · The record

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5 · Who and what money

Authors and funding

6 authors.

Kristina GervinDivision of Clinical Neuroscience, Department of Research and Innovation, Oslo University Hospital, Oslo, Norway. Electronic address: kristina.gervin@farmasi.uio.no.
Magnhild KvernelandDivision of Clinical Neuroscience, National Centre for Epilepsy, Oslo University Hospital, Oslo, Norway.
Karl Otto NakkenDivision of Clinical Neuroscience, National Centre for Epilepsy, Oslo University Hospital, Oslo, Norway.
Knut RudiFaculty of Chemistry, Biotechnology and Food Science, Norwegian University of Life Sciences, Ås, Norway.
Per Ole IversenDepartment of Haematology, Oslo University Hospital, Oslo, Norway; Department of Nutrition, University of Oslo, Oslo, Norway.
Kaja Kristine SelmerDivision of Clinical Neuroscience, Department of Research and Innovation, Oslo University Hospital, Oslo, Norway; Division of Clinical Neuroscience, National Centre for Epilepsy, Oslo University Hospital, Oslo, Norway.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundThe ketogenic diet (KD) is an established treatment for drug-resistant epilepsy. Beyond seizure reduction, many patients report improved energy, cognition, and well-being. DNA methylation (DNAm)-based epigenetic clocks provide molecular indices of biological ageing and may capture short-term adaptations induced by dietary therapy.

methodsFifty-eight adults with drug-resistant epilepsy completed a 12-week modified KD intervention with blood sampling at baseline, four weeks, and 12 weeks. Whole-blood DNAm was profiled using the Illumina EPIC array. Epigenetic ageing was estimated using cumulative clocks (Horvath, Hannum, Levine) and the rate-based DunedinPACE clock. Longitudinal changes were assessed using linear mixed-effects models. DunedinPACE trajectories were clustered using k-means. Associations with β-hydroxybutyrate, seizure frequency, body weight, and health-related quality of life were assessed using correlations and between-cluster comparisons.

findingsAt baseline, participants showed substantial epigenetic age acceleration on cumulative clocks. Cumulative age acceleration did not change during the intervention. In contrast, DunedinPACE revealed two marked ageing-rate trajectories: an initial increase followed by slowing ("up-down") and an initial slowing followed by rebound ("down-up"). Mean ageing rate did not change at the group level (p = 0.18). However, the "up-down" cluster exhibited significantly greater improvement in quality of life compared with the "down-up" cluster (ΔQOLIE 18.8 versus 4.7; p = 0.007) independent of ketosis, seizure reduction, or weight change.

interpretationDrug-resistant epilepsy is associated with increased cumulative epigenetic ageing. While cumulative age remained stable during modified KD therapy, dynamic ageing-rate patterns were linked to patient-reported benefit, suggesting that rate-based DNAm clocks capture short-term systemic adaptation to metabolic treatment.

fundingThis study was funded by the Dam Foundation, the Norwegian Epilepsy Association's Research Fund, the Novo Nordisk Foundation, and the National Advisory Unit on Rare Disorders.

Indexed as

AgingDiet, KetogenicDrug Resistant EpilepsyEpigenesis, GeneticAdultDNA MethylationFemaleHumansMaleMiddle AgedQuality of LifeYoung AdultDunedinPACEEpigenetic ageHealth-related quality of lifeKetogenic dietTreatment refractory epilepsy

Identifiers

PMID42632233
PMCPMC13524883

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.