DNA repair-deficient premature aging models display accelerated epigenetic age.
DNA damage
accelerated aging
epigenetic clock
methylation
progeria
Journal
Aging cell
ISSN: 1474-9726
Titre abrégé: Aging Cell
Pays: England
ID NLM: 101130839
Informations de publication
Date de publication:
22 Dec 2023
22 Dec 2023
Historique:
revised:
20
11
2023
received:
07
04
2023
accepted:
22
11
2023
medline:
23
12
2023
pubmed:
23
12
2023
entrez:
23
12
2023
Statut:
aheadofprint
Résumé
Several premature aging mouse models have been developed to study aging and identify interventions that can delay age-related diseases. Yet, it is still unclear whether these models truly recapitulate natural aging. Here, we analyzed DNA methylation in multiple tissues of four previously reported mouse models of premature aging (Ercc1, LAKI, Polg, and Xpg). We estimated DNA methylation (DNAm) age of these samples using the Horvath clock. The most pronounced increase in DNAm age could be observed in Ercc1 mice, a strain which exhibits a deficit in DNA nucleotide excision repair. Similarly, we detected an increase in epigenetic age in fibroblasts isolated from patients with progeroid syndromes associated with mutations in DNA excision repair genes. These findings highlight that mouse models with deficiencies in DNA repair, unlike other premature aging models, display accelerated epigenetic age, suggesting a strong connection between DNA damage and epigenetic dysregulation during aging.
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
e14058Subventions
Organisme : Schweizerischer Nationalfonds zur Förderung der Wissenschaftlichen Forschung
Informations de copyright
© 2023 The Authors. Aging Cell published by Anatomical Society and John Wiley & Sons Ltd.
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