Slow growth, stress response and aging in Saccharomyces cerevisiae

Abstract

The unicellular organism Saccharomyces cerevisiae was used as a modelsystem to study aging at the cellular level. It is known that limiting the amount of calories used by cells can lead to an extension of lifespan. This thesis shows that by applying controlled slow growth circumstances, cells increase their stress response. Besides the increased stress response, also the substance nicotinamide seems to be involved in facilitating the elongation of lifespan by influencing genetic stability. Limiting the food supply apparently leads to an enhanced agility of the yeast cells. An adequate stress response is essential for cells to survive harsh environmental circumstances. However, the investment in these mechanisms of defence requires resources, which are limited. Cell cycle synchronised cells were analysed for their stress response during the cell cycle. It was found that there were differences on translational and transcriptional level for stress genes during the cell cycle. The effect on the translational response could be due to low protein synthesis rates during the G1-phase. Old and young yeast cells were also compared to each other with respect to their stress response and survival capabilities. It turned out that old cells show a lower stress response than young cells and that after induction by hydrogen peroxide this does not increase much. However, no significant effects were observed on survival, which is rather strange but could be due to insensitivity of the assay. The defence against oxygen radicals can possibly be reinforced by exogenously adding antioxidants. To find potent new antioxidants a screening method was developed using a thioredoxin promoter construct. It was shown that vitamin E and glutathione were able to decrease the reportergene indicating a lowered oxidative stress level