Abstract：
DNA damage represents one of the cell intrinsic causes of stem cell aging, which leads to differentiation-induced removal of damaged stem cells in skin and blood. Dietary restriction (DR) retards aging across various species, including several strains of laboratory mice. Whether, DR has the potential to ameliorate DNA damage-driven stem cell exhaustion remains incompletely understood. In this study, we show that DR strongly extends the time to hair graying in response to γ-irradiation (ionizing radiation [IR])-induced DNA damage of C57BL/6 J mice. The study shows that DR prolongs resting phase of hair follicles. DR-mediated prolongation of hair follicle stem cell (HFSC) quiescence blocks hair growth and prevents the depletion of HFSCs and ckit+ melanoblasts in response to IR. However, prolongation of HFSC quiescence also correlates with a suppression of DNA repair and cannot prevent melanoblast loss and hair graying in the long run, when hair cycling is reinitiated even after extended periods of time. Altogether, these results support a model indicating that nutrient deprivation can delay but not heal DNA damage-driven extinction of melanoblasts by stalling HFSCs in a prolonged state of quiescence coupled with inhibition of DNA repair. Disconnecting these two types of responses to DR could have the potential to delay stem cell aging.
摘要：
DNA损伤是干细胞衰老的细胞内在原因之一，这导致分化诱导的皮肤和血液中受损干细胞的去除。饮食限制（DR）延缓了各种物种的衰老，包括几株实验室老鼠。是否,DR具有改善DNA损伤驱动的干细胞衰竭的潜力仍未完全了解。在这项研究中,我们显示DR强烈延长了响应于γ辐射（电离辐射[IR]）诱导的C57BL/6J小鼠DNA损伤的头发变白的时间。研究表明DR延长了毛囊的静息期。DR介导的毛囊干细胞（HFSC）静止期延长会阻止头发生长，并阻止HFSC和ckit+黑素细胞在IR反应中的消耗。然而,HFSC静止期的延长也与DNA修复的抑制相关，并且从长远来看不能防止黑色素细胞损失和头发变白。即使在延长的时间后，头发循环也会重新开始。总之,这些结果支持了一个模型,该模型表明营养剥夺可以通过使HFSCs在长时间的静止状态下停止并抑制DNA修复来延迟但不能治愈DNA损伤驱动的黑素细胞灭绝.断开这两种对DR的反应可能有延迟干细胞衰老的潜力。
