Molecular genetic analysis of factors that regulate lifespan and immunosenescence in Caenorhabditis elegans

DoctorAging is a mysterious process that almost all the organisms inevitably experience. To explain the cause of aging, many theories of aging, including antagonistic pleiotropy theory and disposable soma theory, have been proposed. Both theories of aging predict that longevity negatively correlates with fitness. However, studies that examined correlations between longevity and early fitness in nature are relatively scarce. Furthermore, the effects of longevity on immune system were poorly understood. In this study, first, I aimed to understand the trade-off between longevity and development using 16 wild-derived C. elegans originated from various geographic areas. I found an inverse correlation between lifespan and developmental rate. In contrast, I did not find such inverse correlation among individuals of wild C. elegans. These results suggest that polymorphic genetic variants influence the negative correlation between longevity and developmental rate to allocate resources to growth and long lifespan. Second, I aimed to understand molecular mechanisms by which longevity affects immunosenescence. I wondered whether genetic mutations that promote longevity proportionally affect the rates of immunosenescence. I found that genetic inhibition of daf-2/insulin/IGF-1 receptor delays and reverses immunosenescence. Both DAF-16/FOXO and HSF-1 transcription factors are required for delayed immunosenescence conferred by daf-2 mutations. Activated DAF-16 and HSF-1 with age further reduced insulin/IGF-1 signaling to boost immunocompetence in old ages. These studies will help to understand the role of aging in organismal fitness