Targeting age-associated decline in brain function with the extracellular vesicle

摘要 裸鼠是一种老鼠大小的啮齿动物，寿命超过30年。考虑到大型哺乳动物 核磁共振比小型哺乳动物活得更长，已经成为研究衰老的一种新的动物模型。它的 超乎寻常的长寿与其他表型有关，如异常产热、极低 癌症发病率、耐低氧能力和 预防阿尔茨海默氏症。我们开发了和 核磁共振诱导的多能干细胞(IPSCs)。核磁共振IPSCs显示了一个特征 形态，表达多能标记，形成类胚体，表现出典型的分化模式， 并分化成三层胚层，但未能形成畸胎瘤。 我们对从核磁共振成纤维细胞中分离的外切体特别感兴趣，因为它们可能具有 核磁共振长寿和抗AD/ADRD的作用。外切体是原始细胞的指纹，可用于转移 遗传物质传给其他生物体。除了包裹在外切体中的遗传物质外， 外切体也携带小分子。 我们的目标是从长寿啮齿动物裸鼠的核磁共振成纤维细胞中分离出携带长寿基因的外切体。 材料转移到小鼠以修改衰老相关的病理，如AD/ADRD，以及 接收鼠标。

ABSTRACT The naked mole rat (NMR) is a mouse-sized rodent that lives over 30 years. Considering that large mammals live longer than small mammals, the NMR has emerged as a novel animal model for aging studies. Its exceptional longevity is associated with other phenotypes, such as unusual thermogenesis, extremely low cancer incidence, resistance to hypoxia, and protected from Alzheimer’s disease. We developed and characterized NMR induced pluripotent stem cells (iPSCs). The NMR iPSCs displayed a characteristic morphology, expressed pluripotent markers, formed embryoid bodies, showed typical differentiation patterns, and differentiated into all three germ layers, but failed to form teratomas. We are particularly interested in exosomes isolated from NMR fibroblasts as they may hold the characteristics of NMR longevity and anti-AD/ADRD. Exosomes are fingerprints of originating cells and feasible to transfer the genetic materials to the other organisms. In addition to the genetic materials encapsulated in exosome, exosome also carry small molecules. We aim to isolate exosomes from NMR fibroblasts of long-living rodent, naked mole rat that carry pro-longevity materials transfer to mouse to modify the aging-associated pathology such as AD/ADRD, and lifespan of the recipient mouse.