The advent of iPSC technology has allowed for the investigation of human diseases directly in the affected human cell type (Marchetto et al., 2011; Mertens et al., 2013a). While this approach appears highly useful for the study of neurodegenerative disorders in patient-specific iPSC derivatives, age-related physiological changes might be one of the most important factors in the development of disease-associated pathologies. Fibroblasts from centenarians can be reprogrammed into iPSCs with telomere size, oxidative damage, and mitochondrial metabolism indistinguishable from embryonic stem cells (Lapasset et al., 2011; Suhr et al., 2010; Takahashi et al., 2007). Further, mesenchymal stem cells reprogrammed into iPSCs and subsequently redifferentiated toward mesenchymal stem cells showed that age-related DNA methylation patterns were erased during reprogramming. In line with our transcriptomic observations in iPSC-derived iNs, iPSC-derived mesenchymal stem cell (MSCs) remained rejuvenated on the methylome level, suggesting that aging signatures might be constantly erased rather than temporarily concealed in iPSCs (Frobel et al., 2014). However, the question of whether the cell-rejuvenating aspect and the dedifferentiation aspect of iPSC reprogramming can be uncoupled remains relevant. Interestingly, some rejuvenating aspects
