Aging stem cells lose the capacity to properly respond to injury and regenerate their residing tissues. Here, we utilized the ability of Drosophila melanogaster 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 foxo and mTOR homologue, Tor as important regulators of GSC quiescence following exposure to ionizing radiation. foxo is required for entry in quiescence, while Tor 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 foxo.

老化的干细胞丧失了对损伤做出适当反应并再生其驻留组织的能力。在这里，我们利用果蝇种系干细胞（GSCs）暴露于低剂量电离辐射（IR）中存活的能力作为成人干细胞损伤的模型，并确定了衰老GSC的再生缺陷： IR，他们无法重新进入细胞周期并不能及时再生种系。从机理上讲，我们将foxo和mTOR同源物Tor视为暴露于电离辐射后GSC静止的重要调节剂。foxo是静态进入所必需的，而Tor对于细胞周期再进入是必不可少的。重要的是，我们进一步表明，IR可以通过丢失狐狸来挽救IR后老化的生殖系干细胞缺乏再生。