Parkinson's disease (PD), the second most common neurodegenerative disease in the world, is characterized by the loss of dopaminergic neurons in the neuromelanin-containing substantia nigra pars compacta (SNpc). Despite observations that melanized neurons are selectively vulnerable to degeneration in PD in an age-dependent manner, the relationship between aging, neuromelanin, and PD remains poorly understood. This study identified novel gene expression signatures of age-dependent and cell type-specific neuromelanin-linked neurotoxicity that may be associated with the pathogenesis of PD. Differential expression analysis between the melanized dopaminergic SNpc and the non-melanized dopaminergic ventral tegmental area (VTA) and correlations of gene expression in the substantia nigra (SN) with age were performed in R. These analyses were validated by studying the selected genes' differential expression in the SN of PD brains. Population-specific expression analysis of the SNpc relative to the VTA revealed that microglia-specific genes were enriched for aging (fold enrichment = 1.51, p = 0.0237) and PD (fold enrichment = 2.36, p = 0.0188), indicating that microglia may provide the link between neuromelanin, aging, and PD. Overall, 37 genes were both differentially expressed in the SNpc relative to the VTA and significantly correlated with age (p < 0.05). In particular, the proteins corresponding to RAB9A, YWHAZ, DTNBP1, and CAT were found to interact with PD-implicated proteins (mean interaction scores 0.493, 0.717, 0.902, 0.581, respectively). These genes could serve as novel preventative and therapeutic drug targets for PD and also be used to develop more accurate rodent models of PD based on neuromelanin-linked neurotoxicity.