Toyama et al., 2013). Thus, one may speculate that heavily damaged nuclear pore complexes would likely impair the function of their interaction partners. By studying normal progressive human aging in fibroblasts, iNs, and the cortex, we have shown that RanBP17 is significantly downregulated with age in several human systems. Strikingly, our results have been further confirmed by several independent GDAC analyses based on a combined 1,200+ samples that also found RanBP17 to be one of the most significantly age-regulated genes in human glioblastomas, kidney, and thyroid carcinomas (summarized in Figure S6). Furthermore, an analysis detected RanBP17 among 14 genes that showed both significant age-correlation and age-dependent differential expression in three independent gene expression platforms (Bozdag et al., 2013). However, the questions of how progressive aging might affect RanBP17 expression, as well as the exact mechanisms of how RanBP17 loss disturbs NCC remain to be explored. While not directly assessed here, in view of the accelerated aging phenotype observed in HGPS, it appears conceivable that a progerin-impaired nuclear envelope structure might allow nuclear leakiness, which could lead to phenotypical cell aging, including DNA damage and deficient response pathways (Musich and Zou, 2009). Most likely, nuclear malformations would also affect the envelope-embedded
