Different gametogenesis states uniquely impact longevity in Caenorhabditis elegans

Reproduction affects lifespan and fat metabolism across species, suggesting a shared regulatory axis. In Caenorhabditis elegans, ablation of germline stem cells leads to extended lifespan and increased fat storage. While many studies focus on germline-less glp-1(e2144) mutants, the hermaphroditic germline of C. elegans provides an excellent opportunity to study how distinct germline anomalies affect lifespan and fat metabolism. We compare metabolomic, transcriptomic, and genetic pathway differences among three sterile mutants: germline-less glp-1, feminized fem-3, and masculinized mog-3. All three accumulate excess fat and share expression changes in stress response and metabolism genes. However, glp-1 mutants exhibit the most robust lifespan extension, fem-3 mutants live longer only at certain temperatures, and mog-3 mutants are markedly short-lived. The extended lifespan in fem-3 mutants require daf-16/FOXO, as in glp-1 mutants. In contrast, daf-16 is dispensable for the already shortened lifespan of mog-3 mutants. Interestingly, mog-3 partially mimics male/mating-induced demise, offering a simplified model to study metabolic and reproductive trade-offs underlying this phenomenon. Our data indicate that disrupting specific germ cell populations leads to distinct and complex physiological and longevity outcomes. These findings highlight the importance of investigating sex-dependent differences and underlying mechanisms to fully understand and potentially modulate these relationships.