Progeria syndromes such as Hutchinson-Gilford progeria syndrome (HGPS) have provided unique opportunities to study cellular processes in the context of accelerated aging (Gordon et al., 2014). The mutations in the nuclear envelope protein LaminA/C (progerin) result in nuclear stiffness and severely altered nuclear architecture, leading to a body-wide phenotype of premature aging (Hennekam, 2006; Scaffidi and Misteli, 2006). While HGPS pathology involves DNA damage and stress-response pathways, the cellular mechanisms that are primarily impaired by progerin, and how they might mimic old cellular age in various tissues remain unknown. Apart from genetically encoded aging, growing evidence has drawn attention to the nuclear pore complex as a primary target for aging in organisms with long lifespans. Nucleoporins have been identified as extremely long-lived low-turnover proteins with very limited capacity for renewal and repair, especially in postmitotic cells (Savas et al., 2012; 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
