Different gametogenesis states uniquely impact longevity inCaenorhabditis elegans

Abstract

AbstractCurtailed reproduction affects lifespan and fat metabolism in diverse organisms, suggesting a regulatory axis between these processes. InCaenorhabditis elegans, ablation of germline stem cells (GSCs) leads to extended lifespan and increased fat accumulation, suggesting GSCs emit signals that modulate systemic physiology. Previous studies mainly focused on the germline-lessglp-1(e2141)mutant, however, the hermaphroditic germline ofC. elegansprovides an excellent opportunity to study the impact of different types of germline anomalies on longevity and fat metabolism. In this study, we compared the metabolomic, transcriptomic, and genetic pathway differences in three sterile mutants: germline-lessglp-1, feminizedfem-3, and masculinizedmog-3. We found that although the three sterile mutants all accumulate excess fat and share expression changes in stress response and metabolism genes, the germline-lessglp-1mutant exhibits the most robust lifespan increase, whereas the feminizedfem-3mutant only lives longer at specific temperatures, and the masculinizedmog-3mutant lives drastically shorter. We demonstrated that overlapping but distinct genetic pathways are required for the longevity of the three different sterile mutants. Our data showed that disruptions of different germ cell populations result in unique and complex physiological and longevity consequences, highlighting exciting avenues for future investigations.