Studies of PTEN, lincRNA, and mitochondrial aconitase for promoting healthy aging in Caenorhabditis elegans

Abstract

Aging is associated with declines in biological functions and various age-associated diseases in living organisms. Aging is affected by multiple factors, including genetic and environmental factors. Although many previous studies have identified various longevity-promoting regimens, one important issue is that longevity does not always increase healthy periods but increases the time of frailty in life. Therefore, an important goal in aging research is to devise proper intervention strategies for increasing this healthy period, while reducing the time of frailty. In this study, I aimed to determine the biological functions of novel genetic factors that regulate healthy aging or immunity using the roundworm Caenorhabditis elegans. First, I identified a PTEN variant that retains longevity without health defects by performing a forward genetic screen using long-lived C. elegans insulin/IGF-1 receptor mutants. Second, by performing a reverse genetic screen, I identified C. elegans long intergenic non-coding RNAs (lincRNAs) that affect the lifespan in wild-type and long-lived C. elegans mutants. Third, I characterized the role of the well-conserved mitochondrial aconitase (ACO-2), a Krebs cycle enzyme that catalyzes the conversion of citrate to isocitrate, in innate immunity of C. elegans. Together, my studies will provide important insights into mechanisms by which novel genetic factors regulate organismal physiology, including aging and immunity. These findings will raise the possibility that PTEN, lincRNA, or mitochondrial aconitase serve as therapeutic targets that promote long and healthy life in humans.