Single-cell immune aging clocks reveal inter-individual heterogeneity during infection and vaccination
Li W, Zhang Z, Kumar S, Botey-Bataller J, Zoodsma M, Ehsani A, Zhan Q, Alaswad A, Zhou L, Grondman I, Koeken V, Yang J, Wang G, Volland S, Crişan T, Joosten L, Illig T, Xu C, Netea M, Li Y
Published in
Nature aging, Page 10.1038/s43587-025-00819-z
Abstract
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.
Open in PubMed