Time flies faster in epilepsy

Time flies faster in epilepsy | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Article Time flies faster in epilepsy Paraskevi Chasani, Mitali Katoch, Johannes R. Lemke, Rami Abou Jamra, and 23 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-7773096/v2 This work is licensed under a CC BY 4.0 License Status: Posted Version 2 posted You are reading this latest preprint version Show more versions Abstract People with epilepsy have reduced life expectancy and increased age-related comorbidities, raising the possibility that epilepsy is associated with accelerated biological aging. Yet, direct and quantitative evidence for biological age acceleration in epilepsy has been limited. Here, we applied a tissue-specific DNA methylation-based epigenetic clock to brain and blood samples from 307 individuals with epilepsy across major etiologies (i.e., structural and genetic) and age groups, alongside 65 nonepileptic controls. Across lesion types and developmental stages, epileptic brain tissue exhibited robust epigenetic age acceleration. In blood, age acceleration was not consistently detected at the group level after controlling for cell composition, chronological age, and sex, although subtle or subgroup-specific effects could not be excluded. Cross-tissue comparisons in structural epilepsies suggested higher age acceleration in brain than in blood overall; however, this pattern was not uniform. Notably, focal cortical dysplasia was the only subgroup showing significant age acceleration in both brain and blood, with no difference between tissues, precluding a general conclusion that the brain universally ages faster than peripheral blood in epilepsy. To assess temporal dynamics, we analyzed an in utero electroporation mouse model of somatic mTOR pathway activation. Mutant epileptic mouse brains recapitulated the human brain aging signatures, with minimal effects in blood and evidence that age acceleration emerged prior to seizure onset. Together, our findings identify epigenetic age acceleration as a core feature of epileptic brain tissue and potential novel treatment target, while highlighting etiological heterogeneity and leaving open the contribution of systemic aging processes in epilepsy. Biological sciences/Neuroscience/Diseases of the nervous system/Epilepsy Health sciences/Diseases/Neurological disorders/Epilepsy aging structural brain lesion SCN1A STXBP1 epigenetic clock DNA methylation Full Text Additional Declarations The authors declare no competing interests. Cite Share Download PDF Status: Posted Version 2 posted You are reading this latest preprint version Show more versions Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. Our growing team is made up of researchers and industry professionals working together to solve the most critical problems facing scientific publishing. Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-7773096","acceptedTermsAndConditions":true,"allowDirectSubmit":true,"archivedVersions":[],"articleType":"Article","associatedPublications":[],"authors":[{"id":526278711,"identity":"5215a39e-10f2-42b0-8d08-a950e49a7494","order_by":0,"name":"Paraskevi Chasani","email":"","orcid":"","institution":"Universitätsklinikum Erlangen","correspondingAuthor":false,"prefix":"","firstName":"Paraskevi","middleName":"","lastName":"Chasani","suffix":""},{"id":526278712,"identity":"9b42213e-7ebf-454a-8f33-5e6e5d4aa9d5","order_by":1,"name":"Mitali Katoch","email":"","orcid":"","institution":"Universitätsklinikum Erlangen","correspondingAuthor":false,"prefix":"","firstName":"Mitali","middleName":"","lastName":"Katoch","suffix":""},{"id":526278713,"identity":"d6e56cb3-a5e6-4438-8e66-1e26a07dd1e7","order_by":2,"name":"Johannes R. 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