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As DNA methylation (DNAm) remodelling is a major ageing marker, we performed genome\u2010wide analysis of DNAm of fibroblasts from healthy, UVSS and CS individuals. Differential analysis highlighted a CS\u2010specific epigenomic signature (progeroid\u2010related; not present in UVSS) enriched in three categories: developmental transcription factors, ion\/neurotransmitter membrane transporters and synaptic neuro\u2010developmental genes. A large fraction of CS\u2010specific DNAm changes were associated with expression changes in CS samples, including in previously reported <jats:italic>post\u2010mortem<\/jats:italic> cerebella. The progeroid phenotype of CS was further supported by epigenomic hallmarks of ageing: the prediction of DNAm of repetitive elements suggested an hypomethylation of <jats:italic>Alu<\/jats:italic> sequences in CS, and the epigenetic clock returned a marked increase in CS biological age respect to healthy and UVSS cells. The epigenomic remodelling of accelerated ageing in CS displayed both commonalities and differences with other progeroid diseases and regular ageing. CS shared DNAm changes with normal ageing more than other progeroid diseases do, and included genes functionally validated for regular ageing. Collectively, our results support the existence of an epigenomic basis of accelerated ageing in CS and unveil new genes and pathways that are potentially associated with the progeroid\/degenerative phenotype.<\/jats:p>","DOI":"10.1111\/acel.13959","type":"journal-article","created":{"date-parts":[[2023,9,9]],"date-time":"2023-09-09T06:12:18Z","timestamp":1694239938000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["Epigenomic signature of accelerated ageing in progeroid Cockayne syndrome"],"prefix":"10.1111","volume":"22","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1243-5311","authenticated-orcid":false,"given":"Cl\u00e9ment","family":"Crochemore","sequence":"first","affiliation":[{"name":"Institut Pasteur, Universit\u00e9 Paris Cit\u00e9, Molecular Mechanisms of Pathological and Physiological Ageing Unit, UMR3738 CNRS  Paris France"},{"name":"Institut Pasteur, Team Stability of Nuclear and Mitochondrial 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