Single-cell immune aging clocks reveal inter-individual heterogeneity during infection and vaccination
Aging affects human immune system functionality, increasing susceptibility to immune-mediated diseases. While gene expression programs accurately reflect immune function, their relationship with biological immune aging and health status remains unclear. Here we developed robust, cell-type-specific aging clocks (sc-ImmuAging) for the myeloid and lymphoid immune cell populations in circulation within peripheral blood mononuclear cells, using single-cell RNA-sequencing data from 1,081 healthy individuals aged from 18 to 97 years. Application of sc-ImmuAging to transcriptome data of patients with COVID-19 revealed notable age acceleration in monocytes, which decreased during recovery. Furthermore, inter-individual variations in immune aging induced by vaccination were identified, with individuals exhibiting elevated baseline interferon response genes showing age rejuvenation in CD8<sup>+</sup> T cells after BCG vaccination. sc-ImmuAging provides a powerful tool for decoding immune aging dynamics, offering insights into age-related immune alterations and potential interventions to promote healthy aging.
Authors
- Inge Grondman (ORCID: https://orcid.org/0000-0002-4687-9845)
- Valerie A. C. M. Koeken (ORCID: https://orcid.org/0000-0002-5783-9013)
- Tania O. Crișan (ORCID: https://orcid.org/0000-0002-3282-5627)
- Martijn Zoodsma (ORCID: https://orcid.org/0000-0003-3636-2209)
- Ahmed Alaswad (ORCID: https://orcid.org/0000-0003-1770-1332)
- Mihai Gheorghe Netea (ORCID: https://orcid.org/0000-0003-2421-6052)
- Jian Yang (ORCID: https://orcid.org/0000-0003-4721-7744)
- Saumya Kumar (ORCID: https://orcid.org/0000-0001-9481-1944)
- Leo A. B. Joosten (ORCID: https://orcid.org/0000-0001-6166-9830)
- Cheng‐Jian Xu (ORCID: https://orcid.org/0000-0003-1586-4672)
- Sonja Volland (ORCID: https://orcid.org/0009-0007-4324-2180)
- Thomas Illig (ORCID: https://orcid.org/0000-0003-4284-5389)
- Qiuyao Zhan
- Javier Botey-Bataller (ORCID: https://orcid.org/0000-0003-3512-3150)
- Gang Wang (ORCID: https://orcid.org/0009-0002-4385-4658)
- Zhenhua Zhang (ORCID: https://orcid.org/0000-0003-2714-0540)
- Wenchao Li (ORCID: https://orcid.org/0000-0002-7956-0742)
- Yang Li (ORCID: https://orcid.org/0000-0003-4022-7341)
- Liang Zhou
- Ali Ehsani (ORCID: https://orcid.org/0000-0003-0745-5852)
Institutions
- University of Bonn (DE)
- Radboud University Nijmegen (NL)
- Capital Medical University (CN)
- Iuliu Hațieganu University of Medicine and Pharmacy (RO)
- Radboud University Medical Center (NL)
- Medizinische Hochschule Hannover (DE)
- Radboud Institute for Molecular Life Sciences (NL)
- Beijing Anding Hospital (CN)
- Helmholtz Centre for Infection Research (DE)
- Centre for Individualised Infection Medicine (DE)
- Center for Experimental and Clinical Infection Research (DE)
- Artificial Intelligence in Medicine (Canada) (CA)
- Rotterdam University of Applied Sciences (NL)
Publication Details
- Journal
- Nature Aging
- Published
- 2025-03-05
- DOI
- https://doi.org/10.1038/s43587-025-00819-z
- Citations
- 29
- Primary Topic
- Circadian rhythm and melatonin
- Type
- article
- Field-Weighted Citation Impact
- 26.52
Funders
- Deutsche Forschungsgemeinschaft
- Radboud Universiteit
- Nederlandse Organisatie voor Wetenschappelijk Onderzoek
- Radboud Universitair Medisch Centrum