A lifespan atlas of the killifish testis defines a pronounced mid-age remodeling shift during testicular aging.

BACKGROUND

Reproductive aging in vertebrates is commonly interpreted as a gradual decline; however, whether aging of the male gonad proceeds linearly or is characterized by periods of accelerated remodeling remains unclear. The turquoise killifish (Nothobranchius furzeri), a short-lived vertebrate, enables lifespan-wide resolution of both rapid germline establishment and subsequent aging within months.

RESULTS

Our staged histological atlas shows that the testis progresses from a simple gonadal primordium to completed spermatogenesis within 3 to 4 weeks post-hatching, revealing an exceptionally compressed developmental program. Proliferative activity peaks in early adulthood, marking maximal spermatogenic output, but declines sharply at mid-age. This period coincides with coordinated repression of germline, mitotic, and meiotic programs and activation of extracellular matrix remodeling, angiogenic, inflammatory, and stromal pathways. These molecular shifts are accompanied by structural remodeling, including expansion of the interstitial compartment and accumulation of collagen-rich matrix. Late-life testes exhibit comparatively modest additional changes, suggesting stabilization of a remodeled, low-proliferative niche.

CONCLUSIONS

Testicular aging in the turquoise killifish unfolds as a process marked by a pronounced mid-age remodeling shift that links testicular decline to somatic niche remodeling. This remodeling window provides a mechanistic entry point for dissecting reproductive aging in a short-lived vertebrate, with potential relevance for comparative studies in other vertebrate systems, although these dynamics may be shaped by species-specific life histories. Together, these findings establish the killifish as a uniquely powerful model for identifying interventions that preserve germline function.