Skip to main content

Single-cell immune aging clocks reveal inter-individual heterogeneity during infection and vaccination.

Nature aging

Authors: Wenchao Li, Zhenhua Zhang, Saumya Kumar, Javier Botey-Bataller, Martijn Zoodsma, Ali Ehsani, Qiuyao Zhan, Ahmed Alaswad, Liang Zhou, Inge Grondman, Valerie Koeken, Jian Yang, Gang Wang, Sonja Volland, Tania O Crişan, Leo A B Joosten, Thomas Illig, Cheng-Jian Xu, Mihai G Netea, Yang Li

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 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.

© 2025. The Author(s).

PMID: 40044970

Participating cluster members