A single-cell transcriptomic landscape characterizes the endocrine system aging in the mouse
Mar. 09, 2026
Prof. Wei Tao published a paper in Protein & Cell with his collaborators.
The endocrine system is crucial for maintaining overall homeostasis. However, its cellular signatures have not been elucidated during aging. Here, we conducted the first-ever single-cell transcriptomic profiles from eight endocrine organs in young and aged mice, revealing the activation of cell-type-specific aging pathways, such as loss of proteostasis, genomic instability and reactive oxygen species (ROS). Among six sex-shared endocrine organs, aging severely impaired gene expression networks in functional endocrine cells, accompanied by enhanced immune infiltration and unfolded protein response (UPR). Mechanism investigations showed that expanded aging-associated exhausted T cells activated MHC-I–UPR axis across functional endocrine cells by releasing GZMK. The inhibition of GZMK receptors by small chemical molecules counteracted the UPR and senescence, suggesting the immune infiltration is a possible driver of endocrine aging. Machine learning identified CD59 as a novel aging feature in sex-shared functional endocrine cells. For two sex-specific endocrine organs, both aged ovaries and testes showed enhanced immune responses. Meanwhile, cell-type-specific aging-associated transcriptional changes revealed an enhanced ROS mainly in aged theca cells of ovaries, while aged spermatogonia in testes showed impaired DNA repair. This study provides a comprehensive analysis of endocrine system aging at single-cell resolution, offering profound insights into mechanisms of endocrine aging.
Original link: https://doi.org/10.1093/procel/pwaf074