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

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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.