The chromatin accessibility signature of human immune aging stems from CD8+ T cells
Open accessAbstract
Aging is linked to deficiencies in immune responses and increased systemic inflammation. To unravel the regulatory programs behind these changes, we applied systems immunology approaches and profiled chromatin accessibility and the transcriptome in PBMCs and purified monocytes, B cells, and T cells. Analysis of samples from 77 young and elderly donors revealed a novel and robust aging signature in PBMCs, with simultaneous systematic chromatin closing at promoters and enhancers associated with T cell signaling and a potentially stochastic chromatin opening mostly found at quiescent and repressed sites. Combined analyses of chromatin accessibility and the transcriptome uncovered immune molecules activated/inactivated with aging and identified the silencing of the IL7R gene and the IL-7 signaling pathway genes as potential biomarkers. This signature is borne by memory CD8+ T cells, which exhibited an aging-related loss in binding of NF-κB and STAT factors. Thus, our study provides a unique and comprehensive approach to identifying candidate biomarkers and provides mechanistic insights into aging-associated immunodeficiency.
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Chromatin accessibility studies in ageing immune cells have demonstrated shifts in chromatin accessibility with age in CD8+ T cells.
“Chromatin accessibility studies in ageing immune cells have demonstrated shifts in chromatin accessibility with age in CD8+ T cells144–147.”
From Measuring biological age using omics data (2022) · cites this paper as [146]
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References 80 · Cited by 200
Research works printed but not linked: 1
- Pawelec G. 2008 Immunosenescence. Springer Science & Business Media, Berlin. 194 pp.
- Authors
- Ucar, D., Márquez, E. J., Chung, C.-H., Marches, R., Rossi, R. J., Uyar, A., Wu, T.-C., George, J., Stitzel, M. L., Palucka, A. K., Kuchel, G. A., & Banchereau, J.
- Affiliations
- University of Connecticut (US)
- The Jackson Laboratory for Genomic Medicine (US)
- Baylor University (US)
- The Jackson Laboratory for Genomic Medicine, Farmington, CT 1
- Corresponding author
- Banchereau, Jacques
- ORCID
- Venue
- Journal of Experimental Medicine
- Publisher
- Rockefeller University Press
- Published
- 2017-09-13
- Volume
- 214
- Issue
- 10
- Pages
- 3123-3144
- ISSN
- 0022-1007 (ISSN-L)
- 1540-9538
- PMC
- PMC5626401
- OpenAlex
- W2755037626
- Cited by
- 200
- References
- 80
- Citations by year
- 2026: 15 · 2025: 20 · 2024: 31 · 2023: 27 · 2022: 24 · 2021: 26 · 2020: 23 · 2019: 11 · 2018: 21 · 2017: 2
- FWCI
- 6.36
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- The Journal of Experimental Medicine (publishedVersion, cc-by-nc-sa)
- PubMed Central (publishedVersion, cc-by-nc-sa)
- PubMed (publishedVersion)
- The Mouseion at the JAXlibrary (Jackson Laboratory) (submittedVersion)
- Funders
- National Institutes of Health (R01 AG048023, P01 AG021600, U19AI089987, R01 AG052608)
- Jackson Laboratory (JAX-DIF-FY15-DU-JB)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics and Chromatin Dynamics
- Life Sciences › Immunology and Microbiology › Immunology › T-cell and B-cell Immunology
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Aging › Genetics, Aging, and Longevity in Model Organisms
- Keywords
- immunosenescence, chromatin accessibility, CD8+ T cells, memory T cells, aging signatures, IL-7 signaling, CD127, NF-κB, systemic inflammation, biomarkers, peripheral blood mononuclear cells
- MeSH terms
- Adult, Aged, Aging, Chromatin, Female, Humans, Leukocytes, Mononuclear, Male, Signal Transduction, Biomarkers, Interleukin-7, CD8-Positive T-Lymphocytes, Epigenesis, Genetic, Interleukin-7 Receptor alpha Subunit, Young Adult
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