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

摘要 裸鼹鼠（NMR）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 寿命比小型哺乳动物长，核磁共振已成为衰老研究的一种新的动物模型。其 异常长寿与其他表型有关，如异常产热，极低的 癌症发病率，耐缺氧性， 防止老年痴呆症我们开发并 表征的NMR诱导的多能干细胞（iPSC）。NMR iPSC显示出一种特征， 形态学上，表达多能性标记，形成胚状体，表现出典型的分化模式， 并分化为所有三个胚层，但未能形成畸胎瘤。 我们对从NMR成纤维细胞中分离的外泌体特别感兴趣，因为它们可能具有 核磁共振寿命和抗AD/ADRD。外泌体是起源细胞的指纹，并且可以将其转移到细胞中。 遗传物质传递给其他生物。除了包裹在外泌体中的遗传物质外， 外泌体也携带小分子。 我们的目标是从长寿啮齿动物裸鼹鼠的NMR成纤维细胞中分离外泌体， 材料转移到小鼠以改变衰老相关的病理学，如AD/ADRD，和小鼠的寿命。 受体小鼠

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.