A Single‐Cell Transcriptome Atlas Characterizes the Immune Landscape of Human Testes During Aging

Aging disrupts immune regulation, affecting tissue function and increasing vulnerability to various diseases. However, the effects of aging on immune cells within human testes are not well understood. In this study, we utilized single-cell RNA sequencing to profile immune cells from 33 human testis samples from individuals aged 21 to 69. Our analysis revealed key immune cell types, including CD8+ T cells, monocytes, cDC2 cells, and various macrophage subtypes within the testes. We observed an age-related change in monocytes and MRC1hi tissue-resident macrophage (TRM), a pattern consistent in both human and mouse testes. Individuals aged 40 and older showed notable shifts in pathways related to phagocytosis, cytokine signaling, and antigen presentation. Monocytes also exhibited pro-inflammatory characteristics, potentially contributing to the low-grade inflammation commonly associated with aging. Together, these findings provide insights into age-related immune cell alterations in human testes and uncover molecular mechanisms underlying these shifts, offering a valuable resource for understanding immune aging in the reproductive system.