Probing control mechanisms of cell cycle and ageing in budding yeast

A modular systems biology approach may be useful to gain a better understanding of complex cellular processes, such as cell cycle and ageing. We show in fact in this review that this approach has been successfully applied to the identification of the long sought molecular mechanism able to set the critical cell size required to enter S phase in budding yeast. It involves two sequential thresholds set by the cyclin dependent kinase inhibitors Far1 and Sic1, that cooperate in carbon source modulation of the critical cell size required to enter S phase, a hallmark of response of the cell cycle to changing growth conditions. After this initial validation, the approach is tested to extract from available literature data a blueprint of ageing in budding yeast. The blueprint newly proposes that the process of ageing is initiated at the level of the yeast cell wall, due to the increase in size of ageing mother cells. This event would result in a mechanical stress of the cell wall that generates a signaling response able to activate two interconnected major cellular responses involved in ageing: stress metabolism and chromatin remodelling. The ensuing new approach to ageing studies is described in comparison with current theories of cell ageing. © 2004 Bentham Science Publishers Ltd.