Research using the killifish Nothobranchius furzeri reveals germ cells orchestrate aging differently by sex through distinct endocrine pathways. Removing germ cells in males enhanced vitamin D signaling and extended lifespan, while the same intervention in females increased IGF-1 signaling, reduced estrogen, and shortened lifespan. This represents a fundamental shift in understanding reproductive aging biology. While invertebrate studies established germ cells accelerate aging uniformly, this vertebrate model demonstrates sex-dependent mechanisms that may explain why females typically outlive males across species. The vitamin D pathway enhancement in germ cell-depleted males suggests reproductive energy reallocation toward cellular maintenance, while the IGF-1 elevation in females indicates metabolic dysregulation without reproductive function. However, findings from a short-lived fish model require validation in mammals before clinical applications. The work challenges the assumption that reproductive cessation universally extends lifespan, instead revealing that longevity effects depend critically on biological sex and underlying hormonal networks. This mechanistic insight could inform sex-specific approaches to healthy aging interventions.