Single cell-resolved cellular, transcriptional and epigenetic changes in T cell populations linked to age-associated immune decline

Splenic T cells play a critical role in the immune system, but their function declines with age. To better understand which aspects of T cell biology are age-perturbed, we performed a multi-time point single cell RNAseq study, along with single cell ATAC seq and single cell TCR sequencing on splenic T cells from mice of various ages. We identified a population of GZMK+ T cells enriched in aged mice, both in CD4+ and CD8+ T cell populations. In addition, we observed a decrease in the T cell repertoire diversity for several specific populations in aged mice. We also identified particular pathways which point to potential mechanisms which perturb T cell function. This study provides new insights into the aging process of splenic T cells, and identifies potential targets for intervention aimed at improving immune function in the elderly.