Regulation of DNA damage signaling by autophagy in senescence.

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Cell senescence is a stable proliferation arrest of damaged cells that prevents the onset of cancer. Paradoxically, cell senescence can also contribute to tissue ageing, by preventing tissue renewal and causing tissue inflammation. Triggers of cell senescence include DNA damage and dysfunctional mitochondria (sites of cellular energy production). Appropriate healthy ageing (i.e. a healthy lifespan without cancer) depends on appropriate balance of the senescence program. Autophagy is a cellular recycling process that degrades and eliminates damaged structures from the cell. Our preliminary data indicates that autophagy serves to suppress accumulation of DNA damage and dysfunctional mitochondria in the cell. Hence, we hypothesise that autophagy controls - and perhaps dampens - onset and/or maintenance of cell senescence, and so tissue and organismal ageing. By exploiting the complementary strengths of Drs. Passos and Adams we will investigate this hypothesis in cell culture and mouse models. Progress in these studies will facilitate development of biomarkers of interventions to promote healthy ageing.