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Gene expression

Can single-cell RNA clocks tell how old your immune system is?

Li W, Zhang Z, Kumar S, et al. · Nature aging · 2025

Open access · cc by · source: Europe PMC

sc-ImmuAging clocks trained on 1,081 healthy adults’ PBMCs showed monocyte age acceleration in COVID-19 that eased with recovery, and CD8+ T-cell rejuvenation after BCG mainly in people with high baseline interferon genes.

Study at a glance

Design
Computational / modelling — Cell-type-specific scRNA-seq aging clocks (sc-ImmuAging) trained on 1,081 healthy adults then applied to COVID-19 and BCG vaccination transcriptomes
N
N=1081 · 1,081 healthy European adults (18–97 years); 864 train / 217 internal validation plus external tests and disease/vaccine applications
Population
Healthy adult PBMC scRNA-seq donors, with separate COVID-19 patient and BCG vaccinee applications
Outcome
Predicted immune biological age vs chronological age (R, RMSE, MAE) and age acceleration in monocytes and CD8+ T cells

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Key findings

Internal and external validation favored the constructed models. COVID-19 patients showed monocyte age acceleration that decreased during recovery. Vaccination effects were heterogeneous: elevated baseline interferon response genes marked CD8+ T-cell age rejuvenation after BCG.

Methodology

Built cell-type-specific transcriptomic clocks for circulating myeloid and lymphoid cells from 1,081 European healthy adults (18–97). Split 80/20 (864/217) for training/internal validation, then applied clocks to COVID-19 and BCG vaccination datasets.

Limitations

Clock residuals are not a proven clinical diagnostic, and observational COVID/vaccine applications cannot prove that changing interferon genes would reverse immune aging.

How this study connects

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