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

Li, Wenchao; Zhang, Zhenhua; Kumar, Saumya; Botey-Bataller, Javier; Zoodsma, Martijn; Ehsani, Ali; Zhan, Qiuyao; Alaswad, Ahmed et al. · Nat Aging · 2025

basic_science · Level V

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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<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.

Medical subject headings