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: 10453353
• 负责人: Sun Hee Yim
• 金额: $ 22.43万
• 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 2024-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10453353
• 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; Blood - brain barrier anatomy; 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; 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; base; 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.

摘要