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BACKGROUND Eukaryotic cells have evolved various response mechanisms to counteract the deleterious consequences of oxidative stress. Among these processes, metabolic alterations seem to play an important role. RESULTS We recently discovered that yeast cells with reduced activity of the key glycolytic enzyme triosephosphate isomerase exhibit an increased(More)
Mitochondrial morphology is regulated in many cultured eukaryotic cells by fusion and fission of mitochondria. A tightly controlled balance between fission and fusion events is required to ensure normal mitochondrial and cellular functions. During ageing, mitochondria are undergoing significant changes on the functional and morphological level. The effect(More)
The mitochondrial theory of ageing proposes that an accumulation of defective mitochondria is a major contributor to the cellular deterioration that underlies the ageing process. The plausibility of the mitochondrial theory depends critically upon the population dynamics of intact and mutant mitochondria in different cell types. Earlier work suggested that(More)
Cells must be able to process multiple information in parallel and, moreover, they must also be able to combine this information in order to trigger the appropriate response. This is achieved by wiring signalling pathways such that they can interact with each other, a phenomenon often called crosstalk. In this study, we employ mathematical modelling(More)
One of the most important antioxidant enzymes is superoxide dismutase (SOD), which catalyzes the dismutation of superoxide radicals to peroxide. The gene for CuZnSOD lies in humans on chromosome 21, and its activity is increased in patients with Down syndrome. However, instead of being beneficial, increased lipid peroxidation is associated with this(More)
Evolution theory indicates that ageing is caused by progressive accumulation of defects, since the evolutionary optimal level of maintenance is always below the minimum required for indefinite survival. Evolutionary theories also suggest that multiple processes are operating in parallel, but unfortunately they make no predictions about specific mechanisms.(More)
The continuing viability of the free-radical theory of ageing has been questioned following apparently incompatible recent results. We show by modelling positional effects of the generation and primary targets of reactive oxygen species that many of the apparently negative results are likely to be misleading. We conclude that there is instead a need to look(More)
Mitochondrial DNA deletions accumulate over the life course in post-mitotic cells of many species and may contribute to aging. Often a single mutant expands clonally and finally replaces the wild-type population of a whole cell. One proposal to explain the driving force behind this accumulation states that random drift alone, without any selection(More)
The mitochondrial theory of aging is widely popular but confronted by several apparent inconsistencies. On the one hand, mitochondrial energy production is of central importance to the health and proper functioning of cells, and single-cell studies have shown that mtDNA deletion mutants accumulate in a clonal fashion in various mammalian species, displacing(More)