ATAC-clock: An aging clock based on chromatin accessibility.

Détails

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Etat: Public
Version: Final published version
Licence: CC BY 4.0
ID Serval
serval:BIB_8F11AE83CAF7
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Institution
Titre
ATAC-clock: An aging clock based on chromatin accessibility.
Périodique
GeroScience
Auteur⸱e⸱s
Morandini F., Rechsteiner C., Perez K., Praz V., Lopez Garcia G., Hinte L.C., von Meyenn F., Ocampo A.
ISSN
2509-2723 (Electronic)
ISSN-L
2509-2723
Statut éditorial
Publié
Date de publication
04/2024
Peer-reviewed
Oui
Volume
46
Numéro
2
Pages
1789-1806
Langue
anglais
Notes
Publication types: Journal Article
Publication Status: ppublish
Résumé
The establishment of aging clocks highlighted the strong link between changes in DNA methylation and aging. Yet, it is not known if other epigenetic features could be used to predict age accurately. Furthermore, previous studies have observed a lack of effect of age-related changes in DNA methylation on gene expression, putting the interpretability of DNA methylation-based aging clocks into question. In this study, we explore the use of chromatin accessibility to construct aging clocks. We collected blood from 159 human donors and generated chromatin accessibility, transcriptomic, and cell composition data. We investigated how chromatin accessibility changes during aging and constructed a novel aging clock with a median absolute error of 5.27 years. The changes in chromatin accessibility used by the clock were strongly related to transcriptomic alterations, aiding clock interpretation. We additionally show that our chromatin accessibility clock performs significantly better than a transcriptomic clock trained on matched samples. In conclusion, we demonstrate that the clock relies on cell-intrinsic chromatin accessibility alterations rather than changes in cell composition. Further, we present a new approach to construct epigenetic aging clocks based on chromatin accessibility, which bear a direct link to age-related transcriptional alterations, but which allow for more accurate age predictions than transcriptomic clocks.
Mots-clé
Humans, Epigenesis, Genetic, Chromatin/genetics, Aging/genetics, DNA Methylation, Gene Expression Profiling, ATAC sequencing, Aging, Biomarker, Chromatin accessibility, Epigenetic clock
Pubmed
Web of science
Open Access
Oui
Création de la notice
10/11/2023 12:10
Dernière modification de la notice
13/02/2024 8:24
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