genes, LAMA3, PCDH10, and RANBP17, to be shared between aging fibroblasts, iNs, and the brain (Figure 5A). We reasoned that potential master regulators of aging might reveal themselves in this category. We became particularly interested in the nuclear pore-associated transport receptor RanBP17, which we found significantly downregulated in the elderly (Figure 5B). For validation of the RNA-seq data for RanBP17, we performed quantitative (q) PCR and western blotting, which both confirmed progressive reduction of RanBP17 with age (Figures 5B and S4). RanBP17 belongs to the importin-β family, which are involved in the transport of nuclear localization signal (NLS)-containing cargo proteins through the nuclear pore complex by binding FG-repeat-containing nucleoporins (Koch et al., 2000; Lee et al., 2010). In line with this, RanBP17 localized as a rim around the nucleus in both fibroblasts and neurons (Figure 5C). To further explore protein levels of RanBP17 in the aging human brain, we paraffin sectioned and immunostained ten of the cortex samples. All of them showed clear staining for βIII-tubulin in cortical neurons in the different layers (Figures 5D and 5E). Immunostaining for RanBP17 showed strong expression in layer II and III neurons of the young adult cortex, whereas it was often barely detectable
