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Chunk #13 — RESULTS — Expression of the Nuclear Pore-Associated Transport Protein RanBP17 during Aging

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Directly Reprogrammed Human Neurons Retain Aging-Associated Transcriptomic Signatures and Reveal Age-Related Nucleocytoplasmic Defects.
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To further explore aging-related changes in gene expression, we performed RNA-seq analysis of 14 human prefrontal cortex samples from 0 up to 89 years of age and analyzed gene expression. First, we noticed that cortical samples consisted of RNA from multiple cell types as they contain large numbers of glial, neuronal, endothelial, and hematopoietic cell-derived transcripts, with neuron-derived RNA being only a minor fraction (Figure S4). We analyzed for differentially expressed aging genes and detected 49 highly significant (padj < 0.05) genes that overlapped between aging iNs and cortex, an overlap 7-fold higher than between iNs and fibroblasts. Further, cortical aging genes were enriched for several similar functional GO/KEGG categories like aging iNs, but also showed enrichment for genes involved in “learning and memory”, “Alzheimer’s disease”, “intracellular transport”, and other categories (Figure S4). Interestingly, we detected only three significant aging 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