Loss of <i>foxo</i> rescues stem cell aging in <i>Drosophila</i> germ line.

Abstract

Aging stem cells lose the capacity to properly respond to injury and regenerate their residing tissues. Here, we utilized the ability of <i>Drosophila melanogaster</i> germline stem cells (GSCs) to survive exposure to low doses of ionizing radiation (IR) as a model of adult stem cell injury and identified a regeneration defect in aging GSCs: while aging GSCs survive exposure to IR, they fail to reenter the cell cycle and regenerate the germline in a timely manner. Mechanistically, we identify <i>foxo</i> and mTOR homologue, <i>Tor</i> as important regulators of GSC quiescence following exposure to ionizing radiation. <i>foxo</i> is required for entry in quiescence, while <i>Tor</i> is essential for cell cycle reentry. Importantly, we further show that the lack of regeneration in aging germ line stem cells after IR can be rescued by loss of <i>foxo</i>.