Single-cell analyses of global cohorts outline determinants of immune aging and link the ratio of GZMK+ to GZMB+ Tem cells to health trajectories

Terekhova M, Kleverov M, Francis T, Artyomov MN, Harridge S, Artomov M

1. 01

   Loss of naive T cells and recent thymic emigrants was the strongest correlate of chronological age

2. 02

   A higher GZMB+ relative to GZMK+ effector-memory CD8 T-cell share marked an unfavorable aging axis

3. 03

   A protein-based surrogate predicted higher mortality and chronic disease over ~a decade in UK Biobank (~50,000 participants)

Study Design

observational_cohort

Sample Size

2,609 subjects

Study Duration

Cross-sectional cohorts; UK Biobank follow-up ~10-17 years (sources differ)

Methodology

Single-cell RNA-seq across 8 cohorts, plasma proteomics in a subset, imputed-model validation in UK Biobank

Limitations

Associations only; UK Biobank lacked CD8 T-cell counts so a proteomic imputation model was used; mainly healthy adults of European and Asian ancestry; blood not tissue; the proposed clinical blood test does not yet exist.