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

Lara Kular; Dennis Klose; Amaya Urdánoz-Casado; Ewoud Ewing; Nuria Planell; David Gomez-Cabrero; Maria Needhamsen; Maja Jagodic

doi:10.3389/fnagi.2022.926468

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

Lara Kular, Dennis Klose, Amaya Urdánoz-Casado, Ewoud Ewing, Nuria Planell, David Gomez-Cabrero, Maria Needhamsen, Maja Jagodic

Research output: Contribution to journal › Article › peer-review

16 Scopus citations

Abstract

Background: 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.

Original language	English (US)
Journal	Frontiers in Aging Neuroscience
Volume	14
DOIs	https://doi.org/10.3389/fnagi.2022.926468
State	Published - Aug 24 2022

Bibliographical note

KAUST Repository Item: Exported on 2022-09-15
Acknowledgements: This 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. The funders of the study had no role in study design, sample acquisition, data collection, data analysis, data interpretation, or writing of the manuscript. 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.

ASJC Scopus subject areas

Cognitive Neuroscience
Aging

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10.3389/fnagi.2022.926468

https://repository.kaust.edu.sa/bitstream/10754/681263/1/fnagi-14-926468.pdf

Cite this

@article{e3cc511105154e74a301f50f4b8669b1,

title = "Epigenetic clock indicates accelerated aging in glial cells of progressive multiple sclerosis patients",

abstract = "Background: 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{\textquoteright}s multi-tissue and Shireby{\textquoteright}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.",

author = "Lara Kular and Dennis Klose and Amaya Urd{\'a}noz-Casado and Ewoud Ewing and Nuria Planell and David Gomez-Cabrero and Maria Needhamsen and Maja Jagodic",

note = "KAUST Repository Item: Exported on 2022-09-15 Acknowledgements: This 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{\textquoteright}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, {\AA}ke Wilberg Foundation, and Karolinska Institute{\textquoteright}s funds. LK was supported by a fellowship from the Margaretha af Ugglas Foundation. DK was supported by an Erasmus fellowship. The funders of the study had no role in study design, sample acquisition, data collection, data analysis, data interpretation, or writing of the manuscript. AU-C was supported by “Doctorados industriales 2018–2020” and “Contrato predoctoral en investigaci{\'o}n en ciencias y tecnolog{\'i}as 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.",

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doi = "10.3389/fnagi.2022.926468",

language = "English (US)",

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T1 - Epigenetic clock indicates accelerated aging in glial cells of progressive multiple sclerosis patients

AU - Kular, Lara

AU - Klose, Dennis

AU - Urdánoz-Casado, Amaya

AU - Ewing, Ewoud

AU - Planell, Nuria

AU - Gomez-Cabrero, David

AU - Needhamsen, Maria

AU - Jagodic, Maja

N1 - KAUST Repository Item: Exported on 2022-09-15 Acknowledgements: This 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. The funders of the study had no role in study design, sample acquisition, data collection, data analysis, data interpretation, or writing of the manuscript. 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.

PY - 2022/8/24

Y1 - 2022/8/24

N2 - Background: 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.

AB - Background: 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.

UR - http://hdl.handle.net/10754/681263

UR - https://www.frontiersin.org/articles/10.3389/fnagi.2022.926468/full

U2 - 10.3389/fnagi.2022.926468

DO - 10.3389/fnagi.2022.926468

M3 - Article

C2 - 36092807

SN - 1663-4365

VL - 14

JO - Frontiers in Aging Neuroscience

JF - Frontiers in Aging Neuroscience

ER -

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

Abstract

Bibliographical note

ASJC Scopus subject areas

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