Continuous turnover and asynchronous aging of human memory T cells across tissues

Heterogeneous subsets of memory T cells including circulating effector memory (TEM) and tissue-resident (TRM) cells in various sites are critical for protection, though their maintenance over age in humans remains poorly understood. Here, we investigated T cell longevity and age-associated dynamics in lymphoid organs and mucosal sites from 10 organ donors over 10 decades of life using epigenetic and transcriptome profiling. Both TEM and TRM showed age-associated loss of DNA methylation though the targets of epigenetic regulation differed between sites. Together, our findings demonstrate distinct modes for memory maintenance by subset and site with tissue residence conferring distinct epigenetic regulation.