Neuronal Stem Cells and Aging

神经干细胞与衰老（8/11） 衰老与对各种疾病的易感性增加和对疾病的抵抗能力下降有关。 组织修复虽然可能涉及许多因素，但有人提出了对较少的解释。 在老年人中经常观察到的从损伤或疾病中完全恢复是指 成体（组织）干细胞的数量或功能。这些细胞在许多组织中持续存在， 它们可以响应生理线索和致病性损伤而增殖和分化。我们 假设虽然神经发生的基础水平随着年龄的增长而下降，但神经发生对 为了治疗的目的，损伤可以恢复到年轻的水平。此外，我们预计，这是 内源性神经发生和来自移植神经元前体神经发生 细胞（NPC）。最后，我们提出，成年人年龄相关性下降的机制 神经发生可以定位于两个区室之一：NPC本身或血管小生境 在其中，他们产生。我们将测试这些假设与以下具体目标：（1）确定如何 衰老改变成年小鼠脑中损伤诱导的神经发生; 2）检查是否与年龄相关 损伤诱导的内源性神经发生的缺陷是由神经元前体细胞（NPC）造成的， （3）评估受体小鼠的年龄在多大程度上改变了受体小鼠的年龄。 确定人胚胎干细胞（hESC）衍生的NPC在损伤后的移植功效; 和（4）确定年龄诱导的损伤诱导的内源性 通过筛选内源性NPC和DG或SVZ蛋白质组的变化进行神经发生 内皮细胞

NEURONAL STEM CELLS AND AGING (8 OF 11) Aging is associated with increased susceptibility to a variety of diseases and diminished capacity for tissue repair. Although many factors are likely to be involved, one proposed explanation for the less complete recovery from injury or disease that is often observed in aged individuals is impairment in the number or function of adult (tissue) stem cells. These cells persist throughout life in many tissues, where they may proliferate and differentiate in response to physiological cues and pathogenic insults. We hypothesize that although basal levels of neurogenesis decline with aging, the neurogenesis response to injury can be restored toward youthful levels for therapeutic purposes. Further, we anticipate that this is the case for both endogenous neurogenesis and neurogenesis from transplanted neuronal precursor cells (NPCs). Finally, we propose that the mechanisms responsible for the age-related decline in adult neurogenesis can be localized to one of two compartments: the NPCs themselves or the vascular niche in which they arise. We will test these hypotheses with the following specific aims: (1) Determine how aging alters injury-induced neurogenesis in the adult mouse brain; 2) Examine whether age-related defects in injury-induced endogenous neurogenesis are imposed by neuronal precursor cells (NPCs) themselves or by their tissue environment; (3) Evaluate the extent to which the age of a recipient mouse determines the transplantation efficacy of human embryonic stem cell (hESC)-derived NPCs after injury; and (4) Identify candidate mediators of the age-induced decline in injury-induced endogenous neurogenesis by screening for changes in the proteome of endogenous NPCs and DG or SVZ endothelial cells.