Investigation of aging (chronological life span) in S. Cerevisiae by systems biology approaches

Abstract

One of the major goals of biological systems research is to improve the human condition and quality of life. Aging is probably the most peculiar phenomenon that a cell, tissue and even an organism experiences. Although it is clear and evident that aging “occurs”, the reasons, pathways and regulators responsible for aging process are still vaguely described. In order to learn more about the biology of aging, studies investigating mechanisms of aging in model organisms such as the budding yeast Saccharomyces cerevisiae may turn out to be relevant to humans. Chronological aging of yeast is especially of interest in regard to mammalian studies since chronologically aged yeast cultures die exhibiting typical markers of apoptosis, accumulate oxygen radicals, and show caspase activation; therefore the chronological aging phenomenon itself may potentially provide insight to the apoptosis mechanism of the cell. The complex structure of signaling networks taking part in aging process results in a necessity for systems biology tools to explore the aging mechanism. Therefore this thesis concentrated upon (i) the reconstruction and topological analysis of the chronological aging network of yeast, (ii) the determination of the effect of metabolic stresses such as medium acidity, carbon limitation and metformin treatment on the chronological aging machinery of yeast via transcriptome analyses, (iii) the integration of the experimental findings with the reconstructed network and to computational analysis of this integrated structure, (iv) the identification of the active proteins and/or protein groups in common during the chronological aging process of yeast created by these different perturbations and (v) the search for potential crosstalks between cellular signaling pathways. Consequently, a more detailed and comprehensive insight of the chronological aging mechanism of yeast is obtained. Results of this thesis provide a solid basis for further research focusing on uncovering agents affecting aging and age-related diseases in humans.