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

利用细胞外囊泡对抗与年龄相关的脑功能衰退

• 批准号: 10659201
• 负责人: Sun Hee Yim
• 金额: $ 18.58万
• 依托单位: TEXAS TECH UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-07-15 至 2025-04-30
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10659201
• 关键词: 3xTg-AD mouse; Age; Age of Onset; Aging; Alzheimer' s Disease; Alzheimer' s disease model; Alzheimer' s disease related dementia; Animal Model; Animals; Behavioral; Biological; Biological Markers; Biological Process; Biology; Blood; Brain; Brain Diseases; Candidate Disease Gene; Cell Death; Cells; Characteristics; Clinical; DNA Methylation; Data; Destinations; Disease; Elderly; Encapsulated; Fibroblasts; Fingerprint; Future; Genetic Materials; Germ Layers; Health; Hypoxia; Incidence; Intervention; Intranasal Administration; Learning; Ligands; Lipid Bilayers; Liver; Longevity; Malignant Neoplasms; Mammals; Measures; Mediating; Membrane; Memory; Modeling; Mole Rats; Molecular; Morphology; Motor Activity; Mus; Neurocognitive; Neurocognitive Deficit; Organ; Organelles; Organism; Oxygen; Pathology; Pathway interactions; Pattern; Performance; Peripheral; Phenotype; Physiological; Physiology; Plasma; Process; Proteins; Resistance; Rodent; Shapes; Surface; Symptoms; Teratoma; Testing; Therapeutic; Thermogenesis; Tissues; Transmission Electron Microscopy; Vesicle; Whole Organism; age related; aged; aging brain; blood-brain barrier crossing; brain cell; cell type; comparative; deprivation; exosome; extracellular vesicles; frailty; functional decline; human subject; improved; indexing; induced pluripotent stem cell; interest; metabolome; novel; protective effect; protein biomarkers; rat genome; receptor; sex; small molecule; symptom treatment; transcriptome; transcriptome sequencing

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.

抽象的 裸鼹鼠 (NMR) 是一种小鼠大小的啮齿动物，与大型哺乳动物相比，寿命超过 30 年。 由于核磁共振比小型哺乳动物寿命更长，因此它已成为衰老研究的新型动物模型。 异常长寿与其他表型相关，例如不寻常的产热作用、极低的寿命 癌症发病率、对缺氧的抵抗力以及 我们开发并预防阿尔茨海默病。 NMR 诱导多能干细胞 (iPSC) 的表征 NMR iPSC 显示出特征。 形态，表达多能标记，形成拟胚体，表现出典型的分化模式， 并分化成所有三个胚层，但未能形成畸胎瘤。 我们对从 NMR 成纤维细胞中分离出的外泌体特别感兴趣，因为它们可能具有以下特征 NMR寿命和抗AD/ADRD的外泌体是原始细胞的指纹并且可以转移。 除了封装在外泌体中的遗传物质外， 外泌体还携带小分子。 我们的目标是从长寿啮齿动物、裸鼹鼠的核磁共振成纤维细胞中分离出外泌体，这些动物具有延长寿命的作用 将材料转移到小鼠体内以改变与衰老相关的病理学，例如AD/ADRD，并延长小鼠的寿命 接收者鼠标。