Nervous system development is a highly complex process involving multiple cellular transitions from that of an embryonic pluripotent state to that of a terminally differentiated neuronal or non-neuronal state. The precise control of gene expression by transcription factors is critical for facilitating the systematic acquisition and maintenance of the appropriate cellular fates. One such essential transcription factor is the RE1-Silencing transcription factor (REST). While most REST studies have been conducted in the context of mammalian embryonic development, recent studies have suggested novel roles for REST in the mature post-natal brain, including the aging human brain. Moreover, REST has been proposed to be neuroprotective during human brain aging, a compelling hypothesis that has not been independently tested. Due to the limitations in obtaining resected fresh human brain tissue for aging research, many research groups have invested in developing alternate in vitro models which involves the conversion of accessible human primary cells, such as dermal fibroblasts, into neurons, using different cellular reprogramming approaches. In my dissertation research, I utilized one particular in vitro model of aging human neurons (also known as induced neurons (iNs) differentiated from dermal fibroblasts using microRNAs) in order to test hypotheses regarding the role of REST in human brain aging.