Epigenomic signature of accelerated ageing in progeroid Cockayne syndrome.
Cockayne syndrome
DNA methylation
UV-sensitive syndrome
ageing
epigenetic clock
progeroid diseases
Journal
Aging cell
ISSN: 1474-9726
Titre abrégé: Aging Cell
Pays: England
ID NLM: 101130839
Informations de publication
Date de publication:
10 2023
10 2023
Historique:
revised:
16
07
2023
received:
17
05
2022
accepted:
31
07
2023
medline:
23
10
2023
pubmed:
9
9
2023
entrez:
9
9
2023
Statut:
ppublish
Résumé
Cockayne syndrome (CS) and UV-sensitive syndrome (UVSS) are rare genetic disorders caused by mutation of the DNA repair and multifunctional CSA or CSB protein, but only CS patients display a progeroid and neurodegenerative phenotype, providing a unique conceptual and experimental paradigm. As DNA methylation (DNAm) remodelling is a major ageing marker, we performed genome-wide analysis of DNAm of fibroblasts from healthy, UVSS and CS individuals. Differential analysis highlighted a CS-specific epigenomic signature (progeroid-related; not present in UVSS) enriched in three categories: developmental transcription factors, ion/neurotransmitter membrane transporters and synaptic neuro-developmental genes. A large fraction of CS-specific DNAm changes were associated with expression changes in CS samples, including in previously reported post-mortem 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 Alu 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.
Identifiants
pubmed: 37688320
doi: 10.1111/acel.13959
pmc: PMC10577576
doi:
Substances chimiques
DNA Repair Enzymes
EC 6.5.1.-
Banques de données
RefSeq
['GSE163841']
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
e13959Informations de copyright
© 2023 The Authors. Aging Cell published by Anatomical Society and John Wiley & Sons Ltd.
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