Neuronal Stem Cells and Aging

神经元干细胞与衰老

• 批准号: 7466669
• 负责人: David Alan Greenberg
• 金额: $ 43.65万
• 依托单位: BUCK INSTITUTE FOR RESEARCH ON AGING
• 依托单位国家: 美国
• 财政年份: 2007
• 资助国家: 美国
• 起止时间: 2007-09-30 至 2012-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7466669
• 关键词: Adult; Age; Aging; Alzheimer' s Disease; Blood Vessels; Brain; Brain Injuries; Brain region; CDKN2A gene; Cell Aging; Cell Death; Cells; Cues; Defect; Disease; Endothelial Cells; Environment; Epilepsy; Fibroblast Growth Factor 2; Hippocampus (Brain); Huntington Disease; Impairment; Individual; Injury; Insulin-Like Growth Factor I; Learning; Life; Localized; Mediator of activation protein; Memory; Molecular; Mus; Neurons; Newborn Infant; Numbers; Physiological; Predisposition; Process; Proliferating; Prosencephalon; Proteome; Purpose; Recovery; Reporting; Screening procedure; Site; Stem cells; Stroke; Testing; Therapeutic; Tissues; Transplantation; Tumor Suppressor Genes; Vascular Endothelial Growth Factors; Wound Healing; adult stem cell; age related; aged; aging brain; cell age; cell motility; dentate gyrus; human embryonic stem cell; neurogenesis; olfactory bulb; pigment epithelium-derived factor; precursor cell; relating to nervous system; response; response to injury

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.

神经干细胞与衰老（11 中的 8） 衰老与多种疾病的易感性增加和自我保护能力下降有关 组织修复。尽管可能涉及许多因素，但有人提出了对较少因素的解释 在老年人中经常观察到的从损伤或疾病中完全康复是指 成体（组织）干细胞的数量或功能。这些细胞终生存在于许多组织中，其中 它们可能会因生理信号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衰老而下降，但神经发生对 出于治疗目的，损伤可以恢复到年轻水平。此外，我们预计这是 内源性神经发生和移植神经元前体的神经发生的情况 细胞（NPC）。最后，我们提出导致成人年龄相关衰退的机制 神经发生可以定位于两个区室之一：NPC 本身或血管生态位 它们出现在其中。我们将通过以下具体目标来检验这些假设：（1）确定如何 衰老会改变成年小鼠大脑中损伤诱导的神经发生； 2）检查是否与年龄有关 损伤引起的内源性神经发生缺陷是由神经元前体细胞（NPC）造成的 自身或组织环境； (3) 评估受体小鼠年龄的程度 确定人胚胎干细胞 (hESC) 来源的 NPC 损伤后的移植效果； (4) 确定年龄引起的损伤引起的内源性衰退的候选调节因子 通过筛选内源性 NPC 和 DG 或 SVZ 蛋白质组的变化来进行神经发生 内皮细胞。