Review Article

Directly Reprogrammed Human Neurons to Understand Age-Related Energy Metabolism Impairment and Mitochondrial Dysfunction in Healthy Aging and Neurodegeneration

Figure 2

Models to study the brain and neuronal aging. Various models have been vital to identifying evolutionarily conserved aging pathways from yeast to animals and model brain physiological aging and neurodegeneration. Invertebrates, such as C. elegans and Drosophila melanogaster, have played a key role in identifying signaling pathways that modulate aging and brain aging across species. In addition, mammalian models have been extensively used to model physiological aging and neurodegeneration. On the one hand, outcome basis studies represent a black box regarding the underlying cellular mechanisms. On the other hand, results obtained from primary murine cultures or immortalized cell lines have proven not reproducible in humans. In contrast, reprogramming fibroblasts from elderly individuals with or without neurogenerative diseases to iPSC-derived neurons or iNs is an attractive model to study cellular and molecular mechanisms of aging human neurons. iPSC-derived neurons lose epigenetic marks associated with aging, while iNs maintain age-specific features from the donor fibroblasts, including metabolic impairments. Moreover, since they are patient or individual-derived fibroblasts, an individual’s genetic and epigenetic aspects are maintained. They can lead towards patient-specific interventions, moving research into the expanding field of personalized and precision medicine.