Studies on the Regulation of Cell Cycle by Glucose Restriction in Trichomonas vaginalis

Restriction of caloric intake is the only non-genetic intervention known to extend the longevity in organisms from yeast to mice and prevents age-dependent deterioration, without causing irreversible developmental or reproductive defects. Previous studies from yeast, worms, flies, and mammals support the idea that CR is not simply a passive effect but an active, highly conserved stress response that evolved early in life’s history to increase an organism’s chance of surviving adversity. Although many dozens of genes have been identified where mutation increases life span, and the molecular pathways and processes that determine the rate of aging are being revealed. The molecular pathways involved in the regulation of life-span are still unclear because of the complex biological organization and regulatory networks in muticellular organisms. We propose to use the single-celled eukaryote Trichomonas vaginalis as a model system to study the longevity interactive network. The advantages of using simpler systems to study the highly conserved phenomenon of calorie restriction include short life span, considerable genetic plasticity, and easier manipulation of the culture condition. Preliminary studies showed that the cell cycle of T. vaginalis can be extended to 9-fold in low glucose medium. Moreover, the well characterized longevity maker genes SIR2 and LAG homologues were upregulated in these cells. The long-lived cells also showed more resistant to oxidative damage compared to the control group. Based on the solid data obtained, we are convinced that T. vaginalis exhibited a longevity interactive network similar to higher eukaryotes. The specific aim of this project is to use T. vaginalis as a model to study longevity induced by glucose restriction with special focus on the role of miRNAs and kinases. Short term research goals include:. (1) Elucidate the dynamics of gene, microRNA, protein and kinase expression profiles during the time course of glucose restriction (2) Bioinformatics analysis of the T. vaginalis longevity interactive network. (3) Experimental validation of identified putative miRNA targets in T. vaginalis. The huge amount of data generated by the present proposal will be used as basis for further studies on other model systems. The simple life-cycle and the ease of handling of this protozoan make it a perfect model to study the longevity interactive network.

Project ID:PC10007-0382
External Project ID:NSC100-2320-B182-015