Age-associated reduction of nuclear protein import in human fibroblasts

• Published in: Biochemical and biophysical research communications Vol. 294; no. 2; pp. 354 - 358
• Main Authors: Pujol, Gemma, Söderqvist, Henrik, Radu, Aurelian
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 07.06.2002
• Subjects: Active Transport, Cell Nucleus - physiology; Adult; Aged; Aged, 80 and over; Ageing; Aging - metabolism; alpha Karyopherins - metabolism; Animals; beta Karyopherins - metabolism; Cell culture; Cell Division; Cells, Cultured; Cellular Apoptosis Susceptibility Protein - metabolism; Child; Exportin 1 Protein; Female; Fibroblasts - cytology; Fibroblasts - metabolism; Genes, Reporter; Human fibroblast; Humans; Karyopherins - genetics; Karyopherins - metabolism; Kidney - metabolism; Lung - metabolism; Male; Mice; Mice, Inbred C57BL; Mouse organs; Nuclear Proteins - metabolism; Nucleocytoplasmic transport; Organ Specificity; Protein Transport - physiology; ran GTP-Binding Protein - metabolism; Receptors, Cytoplasmic and Nuclear; Recombinant Fusion Proteins - biosynthesis; RNA, Messenger - metabolism; Spleen - metabolism; Mouse organs; Cell culture; Human fibroblast; Nucleocytoplasmic transport; Ageing
• ISSN: 0006-291X; 1090-2104
• DOI: 10.1016/S0006-291X(02)00492-8

Age-dependent decreases in the protein concentrations of the nucleocytoplasmic transport factors karyopherin α2, CAS, and RanBP1 were found by comparing fibroblast cultures obtained from young, mature, and old human donors. Karyopherin β1 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.