Regulation of DNA damage signaling by autophagy in senescence.

细胞衰老是受损细胞增殖的稳定停滞，可以防止癌症的发生。矛盾的是，细胞衰老也可以通过阻止组织更新和引起组织炎症来促进组织老化。细胞衰老的诱因包括DNA损伤和功能失调的线粒体（细胞能量产生的部位）。适当的健康衰老（即没有癌症的健康寿命）取决于衰老计划的适当平衡。自噬是一种细胞循环过程，可以降解和消除细胞中受损的结构。我们的初步数据表明，自噬有助于抑制细胞中DNA损伤和功能失调线粒体的积累。因此，我们假设自噬控制——并可能抑制——细胞衰老的开始和/或维持，从而导致组织和有机体衰老。通过利用博士的互补优势。Passos和Adams我们将在细胞培养和小鼠模型中研究这一假设。这些研究的进展将有助于开发干预措施的生物标志物，以促进健康老龄化。

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.