{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,16]],"date-time":"2026-10-16T09:58:13Z","timestamp":1792144693397,"version":"4.4.0"},"reference-count":40,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2023,1,11]],"date-time":"2023-01-11T00:00:00Z","timestamp":1673395200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100002283","name":"Alzheimer's Research UK","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100002283","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000265","name":"Medical Research Council","doi-asserted-by":"publisher","award":["N013255\/1"],"award-info":[{"award-number":["N013255\/1"]}],"id":[{"id":"10.13039\/501100000265","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100013128","name":"Multiple System Atrophy Trust","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100013128","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Neuropathology Appl Neurobio"],"published-print":{"date-parts":[[2023,2]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Aims<\/jats:title>\n                    <jats:p>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.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      We analysed the performances of two DNA methylation\u2010based clocks, DNAmClock\n                      <jats:sub>Multi<\/jats:sub>\n                      and DNAmClock\n                      <jats:sub>Cortical<\/jats:sub>\n                      , in post\u2010mortem WM tissue from multiple subcortical regions and the cerebellum, and in oligodendrocyte\u2010enriched 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 \u03b1\u2010synuclein aggregates in oligodendrocytes.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Estimated DNA methylation (DNAm) ages showed strong correlations with chronological ages, even in WM (e.g., DNAmClock\n                      <jats:sub>Cortical<\/jats:sub>\n                      ,\n                      <jats:italic>r<\/jats:italic>\n                      \u2009=\u2009[0.80\u20130.97],\n                      <jats:italic>p<\/jats:italic>\n                      \u2009&lt;\u20090.05). However, performances and DNAm age estimates differed between clocks and brain regions. DNAmClock\n                      <jats:sub>Multi<\/jats:sub>\n                      significantly underestimated ages in all cohorts except in the MSA prefrontal cortex mixed tissue, whereas DNAmClock\n                      <jats:sub>Cortical<\/jats:sub>\n                      tended towards age overestimations. Pronounced age overestimations in the oligodendrocyte\u2010enriched cohorts (e.g., oligodendrocyte\u2010enriched nuclei,\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u20096.1\u2009\u00d7\u200910\n                      <jats:sup>\u22125<\/jats:sup>\n                      ) suggested that this cell type ages faster. Indeed, significant positive correlations were observed between estimated oligodendrocyte proportions and DNAm age acceleration estimated by DNAmClock\n                      <jats:sub>Cortical<\/jats:sub>\n                      (r\u2009&gt;\u20090.31,\n                      <jats:italic>p<\/jats:italic>\n                      \u2009&lt;\u20090.05), and similar trends were obtained with DNAmClock\n                      <jats:sub>Multi<\/jats:sub>\n                      . Although increased age acceleration was observed in MSA compared with controls, no significant differences were detected upon adjustment for possible confounders (e.g., cell\u2010type proportions).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>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.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/nan.12872","type":"journal-article","created":{"date-parts":[[2022,12,21]],"date-time":"2022-12-21T10:59:41Z","timestamp":1671620381000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":19,"title":["Epigenetic age acceleration is associated with oligodendrocyte proportions in MSA and control brain tissue"],"prefix":"10.1111","volume":"49","author":[{"given":"Megha","family":"Murthy","sequence":"first","affiliation":[{"name":"Queen Square Brain Bank, UCL Queen Square Institute of Neurology University College London  London UK"},{"name":"Department of Clinical and Movement Neurosciences UCL Queen Square Institute of Neurology  London UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gemma","family":"Shireby","sequence":"additional","affiliation":[{"name":"University of Exeter Medical School University of Exeter  Exeter UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yasuo","family":"Miki","sequence":"additional","affiliation":[{"name":"Queen Square Brain Bank, UCL Queen Square Institute of Neurology University College London  London UK"},{"name":"Department of Neuropathology, Institute of Brain Science Hirosaki University Graduate School of Medicine  Hirosaki 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