The mitochondria theory of ageing proposes that the accumulation of somatic mutations in mitochondria DNA during life results in a progressive decline in energetic function and eventual cellular and organism senescence. We propose to test this idea directly, by engineering and expressing a version of the mitochondria DNA polymerise POLG that lacks proofreading exonuclease activity, and hence results in the rapid accumulation of medina mutations. This medina matador will be created and tested in parallel in four model systems: yeast, the mouse, cultured human cells and the fruit fly Drosophilae. The phenotypic consequences of an enhanced rate of accumulation of medina mutations will be investigated via studies of cellular bioenergetics function, ageing-related physiological decline and tissue degeneration, alterations in the pattern of gene expression, and overall lifespan.
Funding SchemeCSC - Cost-sharing contracts
171 76 Stockholm