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Epigenetic age acceleration is associated with oligodendrocyte proportions in MSA and control brain tissue
AIMS: Epigenetic clocks are widely applied as surrogates for biological age in different tissues and/or diseases, including several neurodegenerative diseases. Despite white matter (WM) changes often being observed in neurodegenerative diseases, no study has investigated epigenetic ageing in white m...
Autores principales: | , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
John Wiley and Sons Inc.
2023
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10107510/ https://www.ncbi.nlm.nih.gov/pubmed/36542090 http://dx.doi.org/10.1111/nan.12872 |
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author | Murthy, Megha Shireby, Gemma Miki, Yasuo Viré, Emmanuelle Lashley, Tammaryn Warner, Thomas T. Mill, Jonathan Bettencourt, Conceição |
author_facet | Murthy, Megha Shireby, Gemma Miki, Yasuo Viré, Emmanuelle Lashley, Tammaryn Warner, Thomas T. Mill, Jonathan Bettencourt, Conceição |
author_sort | Murthy, Megha |
collection | PubMed |
description | AIMS: Epigenetic clocks are widely applied as surrogates for biological age in different tissues and/or diseases, including several neurodegenerative diseases. Despite white matter (WM) changes often being observed in neurodegenerative diseases, no study has investigated epigenetic ageing in white matter. METHODS: We analysed the performances of two DNA methylation‐based clocks, DNAmClock(Multi) and DNAmClock(Cortical), in post‐mortem WM tissue from multiple subcortical regions and the cerebellum, and in oligodendrocyte‐enriched nuclei. We also examined epigenetic ageing in control and multiple system atrophy (MSA) (WM and mixed WM and grey matter), as MSA is a neurodegenerative disease comprising pronounced WM changes and α‐synuclein aggregates in oligodendrocytes. RESULTS: Estimated DNA methylation (DNAm) ages showed strong correlations with chronological ages, even in WM (e.g., DNAmClock(Cortical), r = [0.80–0.97], p < 0.05). However, performances and DNAm age estimates differed between clocks and brain regions. DNAmClock(Multi) significantly underestimated ages in all cohorts except in the MSA prefrontal cortex mixed tissue, whereas DNAmClock(Cortical) tended towards age overestimations. Pronounced age overestimations in the oligodendrocyte‐enriched cohorts (e.g., oligodendrocyte‐enriched nuclei, p = 6.1 × 10(−5)) suggested that this cell type ages faster. Indeed, significant positive correlations were observed between estimated oligodendrocyte proportions and DNAm age acceleration estimated by DNAmClock(Cortical) (r > 0.31, p < 0.05), and similar trends were obtained with DNAmClock(Multi). Although increased age acceleration was observed in MSA compared with controls, no significant differences were detected upon adjustment for possible confounders (e.g., cell‐type proportions). CONCLUSIONS: Our findings show that oligodendrocyte proportions positively influence epigenetic age acceleration across brain regions and highlight the need to further investigate this in ageing and neurodegeneration. |
format | Online Article Text |
id | pubmed-10107510 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | John Wiley and Sons Inc. |
record_format | MEDLINE/PubMed |
spelling | pubmed-101075102023-04-18 Epigenetic age acceleration is associated with oligodendrocyte proportions in MSA and control brain tissue Murthy, Megha Shireby, Gemma Miki, Yasuo Viré, Emmanuelle Lashley, Tammaryn Warner, Thomas T. Mill, Jonathan Bettencourt, Conceição Neuropathol Appl Neurobiol Original Articles AIMS: Epigenetic clocks are widely applied as surrogates for biological age in different tissues and/or diseases, including several neurodegenerative diseases. Despite white matter (WM) changes often being observed in neurodegenerative diseases, no study has investigated epigenetic ageing in white matter. METHODS: We analysed the performances of two DNA methylation‐based clocks, DNAmClock(Multi) and DNAmClock(Cortical), in post‐mortem WM tissue from multiple subcortical regions and the cerebellum, and in oligodendrocyte‐enriched nuclei. We also examined epigenetic ageing in control and multiple system atrophy (MSA) (WM and mixed WM and grey matter), as MSA is a neurodegenerative disease comprising pronounced WM changes and α‐synuclein aggregates in oligodendrocytes. RESULTS: Estimated DNA methylation (DNAm) ages showed strong correlations with chronological ages, even in WM (e.g., DNAmClock(Cortical), r = [0.80–0.97], p < 0.05). However, performances and DNAm age estimates differed between clocks and brain regions. DNAmClock(Multi) significantly underestimated ages in all cohorts except in the MSA prefrontal cortex mixed tissue, whereas DNAmClock(Cortical) tended towards age overestimations. Pronounced age overestimations in the oligodendrocyte‐enriched cohorts (e.g., oligodendrocyte‐enriched nuclei, p = 6.1 × 10(−5)) suggested that this cell type ages faster. Indeed, significant positive correlations were observed between estimated oligodendrocyte proportions and DNAm age acceleration estimated by DNAmClock(Cortical) (r > 0.31, p < 0.05), and similar trends were obtained with DNAmClock(Multi). Although increased age acceleration was observed in MSA compared with controls, no significant differences were detected upon adjustment for possible confounders (e.g., cell‐type proportions). CONCLUSIONS: Our findings show that oligodendrocyte proportions positively influence epigenetic age acceleration across brain regions and highlight the need to further investigate this in ageing and neurodegeneration. John Wiley and Sons Inc. 2023-01-11 2023-02 /pmc/articles/PMC10107510/ /pubmed/36542090 http://dx.doi.org/10.1111/nan.12872 Text en © 2022 The Authors. Neuropathology and Applied Neurobiology published by John Wiley & Sons Ltd on behalf of British Neuropathological Society. https://creativecommons.org/licenses/by/4.0/This is an open access article under the terms of the http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited. |
spellingShingle | Original Articles Murthy, Megha Shireby, Gemma Miki, Yasuo Viré, Emmanuelle Lashley, Tammaryn Warner, Thomas T. Mill, Jonathan Bettencourt, Conceição Epigenetic age acceleration is associated with oligodendrocyte proportions in MSA and control brain tissue |
title | Epigenetic age acceleration is associated with oligodendrocyte proportions in MSA and control brain tissue |
title_full | Epigenetic age acceleration is associated with oligodendrocyte proportions in MSA and control brain tissue |
title_fullStr | Epigenetic age acceleration is associated with oligodendrocyte proportions in MSA and control brain tissue |
title_full_unstemmed | Epigenetic age acceleration is associated with oligodendrocyte proportions in MSA and control brain tissue |
title_short | Epigenetic age acceleration is associated with oligodendrocyte proportions in MSA and control brain tissue |
title_sort | epigenetic age acceleration is associated with oligodendrocyte proportions in msa and control brain tissue |
topic | Original Articles |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10107510/ https://www.ncbi.nlm.nih.gov/pubmed/36542090 http://dx.doi.org/10.1111/nan.12872 |
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