TY - JOUR
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 -