title: Age-associated reduction of nuclear protein import in human fibroblasts.
abstract: Age-dependent decreases in the protein concentrations of the nucleocytoplasmic transport factors karyopherin alpha2, CAS, and RanBP1 were found by comparing fibroblast cultures obtained from young, mature, and old human donors. Karyopherin beta1 levels do not change with age and present very little variation among donors. The decrease in the concentration of transport factors is accompanied by a reduction in the protein import rate in fibroblasts from old donors, as detected by a change in the intracellular localization of a test transport substrate that shuttles between the cytoplasm and the nucleus. Measurements of concentrations of the same import factors in organs and tissues of old mice revealed a decrease of CAS in kidney, lung, and spleen. The import reduction in old age is expected to lead to impaired activity of proteins whose functions depend on timely import into the nuclei.
authors.affiliation: Carl C. Icahn Institute for Gene Therapy and Molecular Medicine, Mount Sinai School of Medicine, New York, NY 10029, USA.
authors.forename: Gemma
authors.initials: G
authors.lastname: Pujol
authors.forename: Henrik
authors.initials: H
authors.lastname: Söderqvist
authors.forename: Aurelian
authors.initials: A
authors.lastname: Radu
mesh_terms: D021581:Active Transport, Cell Nucleus / Q000502:physiology*; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000375:Aging / Q000378:metabolism*; D000818:Animals; D002455:Cell Division; D002478:Cells, Cultured; D029563:Cellular Apoptosis Susceptibility Protein / Q000378:metabolism; D002648:Child; D005260:Female; D005347:Fibroblasts / Q000166:cytology / Q000378:metabolism*; D017930:Genes, Reporter; D006801:Humans; D028884:Karyopherins / Q000235:genetics / Q000378:metabolism; D007668:Kidney / Q000378:metabolism; D008168:Lung / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009687:Nuclear Proteins / Q000378:metabolism; D009928:Organ Specificity; D021381:Protein Transport / Q000502:physiology*; D012333:RNA, Messenger / Q000378:metabolism; D018160:Receptors, Cytoplasmic and Nuclear; D011993:Recombinant Fusion Proteins / Q000096:biosynthesis; D013154:Spleen / Q000378:metabolism; D028901:alpha Karyopherins / Q000378:metabolism; D028961:beta Karyopherins / Q000378:metabolism; D020931:ran GTP-Binding Protein / Q000378:metabolism; D000097606:Exportin 1 Protein
chemical_list: D029563:Cellular Apoptosis Susceptibility Protein; D028884:Karyopherins; D009687:Nuclear Proteins; D012333:RNA, Messenger; D018160:Receptors, Cytoplasmic and Nuclear; D011993:Recombinant Fusion Proteins; D028901:alpha Karyopherins; D028961:beta Karyopherins; D020931:ran GTP-Binding Protein; D000097606:Exportin 1 Protein; C424166:KPNB1 protein, human; C087978:karyopherin alpha 2; C091775:ran-binding protein 1