--- res: bibo_abstract: - Aging is a major risk factor for many human diseases, and in vitro generation of human neurons is an attractive approach for modeling aging-related brain disorders. However, modeling aging in differentiated human neurons has proved challenging. We generated neurons from human donors across a broad range of ages, either by iPSC-based reprogramming and differentiation or by direct conversion into induced neurons (iNs). While iPSCs and derived neurons did not retain aging-associated gene signatures, iNs displayed age-specific transcriptional profiles and revealed age-associated decreases in the nuclear transport receptor RanBP17. We detected an age-dependent loss of nucleocytoplasmic compartmentalization (NCC) in donor fibroblasts and corresponding iNs and found that reduced RanBP17 impaired NCC in young cells, while iPSC rejuvenation restored NCC in aged cells. These results show that iNs retain important aging-related signatures, thus allowing modeling of the aging process in vitro, and they identify impaired NCC as an important factor in human aging.@eng bibo_authorlist: - foaf_Person: foaf_givenName: Jerome foaf_name: Mertens, Jerome foaf_surname: Mertens - foaf_Person: foaf_givenName: Apuã C.M. foaf_name: Paquola, Apuã C.M. foaf_surname: Paquola - foaf_Person: foaf_givenName: Manching foaf_name: Ku, Manching foaf_surname: Ku - foaf_Person: foaf_givenName: Emily foaf_name: Hatch, Emily foaf_surname: Hatch - foaf_Person: foaf_givenName: Lena foaf_name: Böhnke, Lena foaf_surname: Böhnke - foaf_Person: foaf_givenName: Shauheen foaf_name: Ladjevardi, Shauheen foaf_surname: Ladjevardi - foaf_Person: foaf_givenName: Sean foaf_name: McGrath, Sean foaf_surname: McGrath - foaf_Person: foaf_givenName: Benjamin foaf_name: Campbell, Benjamin foaf_surname: Campbell - foaf_Person: foaf_givenName: Hyungjun foaf_name: Lee, Hyungjun foaf_surname: Lee - foaf_Person: foaf_givenName: Joseph R. foaf_name: Herdy, Joseph R. foaf_surname: Herdy - foaf_Person: foaf_givenName: J. Tiago foaf_name: Gonçalves, J. Tiago foaf_surname: Gonçalves - foaf_Person: foaf_givenName: Tomohisa foaf_name: Toda, Tomohisa foaf_surname: Toda - foaf_Person: foaf_givenName: Yongsung foaf_name: Kim, Yongsung foaf_surname: Kim - foaf_Person: foaf_givenName: Jürgen foaf_name: Winkler, Jürgen foaf_surname: Winkler - foaf_Person: foaf_givenName: Jun foaf_name: Yao, Jun foaf_surname: Yao - foaf_Person: foaf_givenName: Martin W foaf_name: HETZER, Martin W foaf_surname: HETZER foaf_workInfoHomepage: http://www.librecat.org/personId=86c0d31b-b4eb-11ec-ac5a-eae7b2e135ed orcid: 0000-0002-2111-992X - foaf_Person: foaf_givenName: Fred H. foaf_name: Gage, Fred H. foaf_surname: Gage bibo_doi: 10.1016/j.stem.2015.09.001 bibo_issue: '6' bibo_volume: 17 dct_date: 2015^xs_gYear dct_isPartOf: - http://id.crossref.org/issn/1934-5909 dct_language: eng dct_publisher: Elsevier@ dct_subject: - Cell Biology - Genetics - Molecular Medicine dct_title: Directly reprogrammed human neurons retain aging-associated transcriptomic signatures and reveal age-related nucleocytoplasmic defects@ fabio_hasPubmedId: '26456686' ...