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Epigenetic clock indicates accelerated aging in glial cells of progressive multiple sclerosis patients

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dc.contributor.authorKular, Lara
dc.contributor.authorKlose, Dennis
dc.contributor.authorUrdánoz Casado, Amaya
dc.contributor.authorEwing, Ewoud
dc.contributor.authorPlanell, Nuria
dc.contributor.authorGómez-Cabrero, David
dc.contributor.authorNeedhamsen, Maria
dc.contributor.authorJagodic, Maja
dc.contributor.departmentCiencias de la Saludes_ES
dc.contributor.departmentOsasun Zientziakeu
dc.contributor.funderGobierno de Navarra / Nafarroako Gobernuaes
dc.date.accessioned2022-12-30T12:46:46Z
dc.date.available2022-12-30T12:46:46Z
dc.date.issued2022
dc.date.updated2022-12-30T12:17:10Z
dc.description.abstractBackground: Multiple sclerosis (MS) is a chronic inflammatory neurodegenerative disease of the central nervous system (CNS) characterized by irreversible disability at later progressive stages. A growing body of evidence suggests that disease progression depends on age and inflammation within the CNS. We aimed to investigate epigenetic aging in bulk brain tissue and sorted nuclei from MS patients using DNA methylation-based epigenetic clocks. Methods: We applied Horvath’s multi-tissue and Shireby’s brain-specific Cortical clock on bulk brain tissue (n = 46), sorted neuronal (n = 54), and glial nuclei (n = 66) from post-mortem brain tissue of progressive MS patients and controls. Results: We found a significant increase in age acceleration residuals, corresponding to 3.6 years, in glial cells of MS patients compared to controls (P = 0.0024) using the Cortical clock, which held after adjustment for covariates (Padj = 0.0263). The 4.8-year age acceleration found in MS neurons (P = 0.0054) did not withstand adjustment for covariates and no significant difference in age acceleration residuals was observed in bulk brain tissue between MS patients and controls. Conclusion: While the findings warrant replication in larger cohorts, our study suggests that glial cells of progressive MS patients exhibit accelerated biological aging.en
dc.description.sponsorshipThis study was supported by grants from the Swedish Research Council, the Swedish Association for Persons with Neurological Disabilities, the Swedish Brain Foundation, the Swedish MS Foundation, the Stockholm County Council – ALF project, the European Union’s Horizon 2020 research, innovation program (grant agreement No. 733161) and the European Research Council (ERC, grant agreement No. 818170), the Knut and Alice Wallenberg Foundation grant, Åke Wilberg Foundation, and Karolinska Institute’s funds. LK was supported by a fellowship from the Margaretha af Ugglas Foundation. DK was supported by an Erasmus fellowship. AU-C was supported by “Doctorados industriales 2018–2020” and “Contrato predoctoral en investigación en ciencias y tecnologías de la salud en el periodo 2019–2022” fellowships, both funded by the Government of Navarra and by an Erasmus fellowship. The computations were enabled by resources provided by the Swedish National Infrastructure for Computing (SNIC) at UPPMAX, partially funded by the Swedish Research Council through grant agreement No. 2018-05973.en
dc.format.mimetypeapplication/pdfen
dc.identifier.citationKular, L., Klose, D., Urdánoz-Casado, A., Ewing, E., Planell, N., Gomez-Cabrero, D., Needhamsen, M., & Jagodic, M. (2022). Epigenetic clock indicates accelerated aging in glial cells of progressive multiple sclerosis patients. Frontiers in Aging Neuroscience, 14, 926468.en
dc.identifier.doi10.3389/fnagi.2022.926468
dc.identifier.issn1663-4365
dc.identifier.urihttps://academica-e.unavarra.es/handle/2454/44535
dc.language.isoengen
dc.publisherFrontiers Mediaen
dc.relation.ispartofFrontiers in Aging Neuroscience 14:926468en
dc.relation.publisherversionhttps://doi.org/10.3389/fnagi.2022.926468
dc.rights© 2022 Kular, Klose, Urdánoz-Casado, Ewing, Planell, Gomez-Cabrero, Needhamsen and Jagodic. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.en
dc.rights.accessRightsAcceso abierto / Sarbide irekiaes
dc.rights.accessRightsinfo:eu-repo/semantics/openAccessen
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/
dc.subjectAgingen
dc.subjectBrainen
dc.subjectDNA methylationen
dc.subjectEpigenetic clocken
dc.subjectGlial cellsen
dc.subjectMultiple sclerosisen
dc.subjectNeuronsen
dc.titleEpigenetic clock indicates accelerated aging in glial cells of progressive multiple sclerosis patientsen
dc.typeArtículo / Artikuluaes
dc.typeinfo:eu-repo/semantics/articleen
dc.type.versionVersión publicada / Argitaratu den bertsioaes
dc.type.versioninfo:eu-repo/semantics/publishedVersionen
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relation.isAuthorOfPublication.latestForDiscoveryc0cb79d9-6664-4b47-bcd1-b7cb133d224e

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