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The chromatin accessibility signature of human immune aging stems from CD8+ T cells

Aging is linked to deficiencies in immune responses and increased systemic inflammation. To unravel the regulatory programsbehind these changes, we applied systems immunology approaches and profiled chromatin accessibility and the transcriptomein PBMCs, purified monocytes, and B and T cells. Analysis of samples from 77 young and elderly donors revealed a novel androbust aging signature in PBMCs, with simultaneous systematic chromatin closing at promoters and enhancers associated withT cell signaling and a potentially stochastic chromatin opening mostly found at quiescent and repressed sites. Combined analysesof chromatin accessibility and the transcriptome uncovered immune molecules activated/inactivated with aging andidentified the silencing of the IL7R gene and the IL-7 signaling pathway genes as potential biomarkers. This signature is borneby memory CD8+ T cells, which exhibited an aging-related loss in binding of NF-κB and STAT factors. Thus, our study providesa unique and comprehensive approach to identifying candidate biomarkers and provides mechanistic insights into aging-associatedimmunodeficiency.

Click on a Dataset ID in the table below to learn more, and to find out who to contact about access to these data

Dataset ID Description Technology Samples
EGAD00001003602 Illumina HiSeq 2500 273
Publications Citations
The chromatin accessibility signature of human immune aging stems from CD8<sup>+</sup> T cells.
J Exp Med 214: 2017 3123-3144
106
Multiomic Profiling Identifies cis-Regulatory Networks Underlying Human Pancreatic β Cell Identity and Function.
Cell Rep 26: 2019 788-801.e6
43
Sexual-dimorphism in human immune system aging.
Nat Commun 11: 2020 751
236
CoRE-ATAC: A deep learning model for the functional classification of regulatory elements from single cell and bulk ATAC-seq data.
PLoS Comput Biol 17: 2021 e1009670
4
Gene Expression Analysis Reveals Age and Ethnicity Signatures Between Young and Old Adults in Human PBMC.
Front Aging 2: 2021 797040
1