GERMLINE LONGEVITY · Germline-mediated regulation of lifespan in worms and fish

Trade-offs between reproduction and lifespan are observed in many organisms, however little is known about their underlying molecular and cellular mechanisms. In C. elegans, when germ cell precursors are removed by laser microsurgery, animals live up to 60% longer than normal. This longevity is not a simple consequence of sterility, as removing the entire gonad does not extend lifespan, suggesting that the germline and somatic gonad produce opposing signals that are pro-aging and anti-aging, respectively. Molecular genetic studies suggested that proliferating germline stem cells produce pro-aging effects. Recent studies revealed that lifespan extension upon reduced germline activities depends on the functions of several transcription factors, which regulate lipolysis, fatty acid desaturation and autophagy in somatic cells. Although a clearer picture of the anti-aging activities in somatic cells is emerging, the origin and characteristics of the pro-aging signals in the proliferating germline stem cells is totally unknown. In addition, the direct involvement of germ cells and/or germline stem cells in vertebrate lifespan has not been addressed. Using germline-specific knockdown system and transcriptome data in germline, I will perform RNAi screening and identify the signal emanating from germline stem cells to regulate lifespan in C. elegans. In parallel, I will use a vertebrate model medaka (Oryzias latipes) for comparative analysis of germline longevity, since germline stem cells and several germline mutants are well characterized. I will examine the lifespan, stress resistance, gene expression and metabolic change using several germline mutants. These studies will not only greatly contribute to the further understanding of germline longevity pathway but also should shed light on whether this pathway is conserved in vertebrates. This work will potentially contribute to a better understanding of the relationship between reproduction and lifespan in humans.