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Age-associated decline in cdk1 activity delays cell cycle progression of human T lymphocytes

Boutet, S
Published in Journal of Immunology. 1998, vol. 161, no. 10, p. 5203-9
Abstract Despite the repeatedly observed impaired proliferative response of T lymphocytes from aged donors, the precise molecular basis underlying such a defect is still poorly understood. The aim of this study was to determine whether cyclin-dependent kinase 1 (cdk1), a serine-threonine kinase required for entry into mitosis, is implicated in this age-associated dysregulation of the cell cycle. T lymphocytes derived from young and elderly donors were blocked in S phase by hydroxyurea after a 48-h activation by anti-CD3 Abs. Under these experimental conditions, only the cells that were already located beyond the S phase were able to complete the cell cycle, decreasing their DNA content from 4n to 2n chromosomes. Using this procedure, a delay in the accomplishment of mitosis could be observed in cells from elderly individuals, as evidenced by propidium iodide staining. In this age group, only a minimal cdk1 activity could be immunoprecipitated from cells sorted in G2/M after nocodazole block. The decrease in cdk1 activity observed in T lymphocytes from aged donors could be accounted for by at least three mechanisms: 1) a failure of these cells to express a sufficient amount of cdk1, 2) a reduced level of the associated cyclin B1, and 3) an incomplete dephosphorylation of the kinase on tyrosine. This low cdk1 activity is likely to postpone the progression through the G2/M transition and participates in the dysfunction of the cell cycle during the process of aging.
Keywords AdultAgedAged, 80 and overAging/immunologyAntibodies, Monoclonal/pharmacologyAntigens, CD3/immunologyCDC2 Protein Kinase/biosynthesis/metabolismCell Cycle/immunologyCyclin B/biosynthesisCyclin B1Enzyme Activation/drug effects/immunologyG2 Phase/immunologyHumansInterleukin-2/pharmacologyLymphocyte Activation/drug effectsMacromolecular SubstancesMitosis/immunologyPhosphorylationT-Lymphocytes/cytology/enzymology/immunology
PMID: 9820491
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Other version: http://www.jimmunol.org/content/161/10/5203.full
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QUADRI DEFILIPPIS, Rafael et al. Age-associated decline in cdk1 activity delays cell cycle progression of human T lymphocytes. In: Journal of Immunology, 1998, vol. 161, n° 10, p. 5203-9. https://archive-ouverte.unige.ch/unige:16931

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