ATAC-clock: An aging clock based on chromatin accessibility.
Details
Serval ID
serval:BIB_8F11AE83CAF7
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
ATAC-clock: An aging clock based on chromatin accessibility.
Journal
GeroScience
ISSN
2509-2723 (Electronic)
ISSN-L
2509-2723
Publication state
Published
Issued date
04/2024
Peer-reviewed
Oui
Volume
46
Number
2
Pages
1789-1806
Language
english
Notes
Publication types: Journal Article
Publication Status: ppublish
Publication Status: ppublish
Abstract
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.
Keywords
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
Yes
Create date
10/11/2023 11:10
Last modification date
13/02/2024 7:24