Age-related decline in niche self-renewal factors drives testis aging via Hairless, Imp, and Chinmo

Aging tissues lose function in part because stem cells change in number and behavior, but how age-related changes in the stem cell niche drive these processes is not well understood. Using the fruit fly testis, we asked how aging of the niche microenvironment influences stem cell maintenance and competition. We show that levels of niche cell-derived bone morphogenetic protein (BMP) signals decline with age, leading to increased expression of the transcriptional corepressor Hairless in germline stem cells (GSCs). Elevated Hairless reduces the RNA binding protein Imp, causing loss of the stem cell factor Chinmo and triggering abnormal extracellular matrix accumulation, stem cell displacement, and niche deterioration. Overexpressing BMP signals in the niche, up-regulating Imp in GSCs, or depleting Hairless in GSCs ameliorate multiple aging-related defects. In contrast, GSC clones with low Imp or high Hairless outcompete their neighbors and take over the niche. These findings reveal how aging niche signals affect tissue decline and stem cell residence.