Cell proliferation and ku protein expression in ageing humans.
Previous studies on DNA repair in ageing have demonstrated increased frequencies of single and double strand breaks in lymphocytes from elderly subjects and, as a consequence, decreased efficiency in DNA replication. We have investigated the relationship between cell proliferation and the nuclear expression of ku protein in a human population of 43 subjects of different ages. Ku is an heterodimeric protein composed of two subunits of 70 and 80 kDa, which is involved in the early steps of DNA damage recognition. In the present study, PBL from subjects of different ages were PHA-activated to evaluate the stimulation index and the production of Th1- and Th2-type cytokines. Moreover, nuclear extracts were obtained from activated lymphocytes to evaluate by a gel retardation assay the presence and the functional activity of the heterodimer ku 70/80. Our results indicate that ageing affects the mitotic responsiveness and cytokine production to a significant extent, but only marginally the expression of ku 70/80. These findings suggest that the age-related impairment in DNA repair mechanisms are only in part related to the reduced expression of ku protein able to recognize DNA damage.
Frasca
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Laboratory of Immunology, ENEA CR Casaccia, Rome, Italy. frasca@casaccia.enea.it
Barattini
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P
Goso
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Pucci
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Rizzo
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G
Bartoloni
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Costanzo
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M
Errani
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Guidi
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Antico
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Tricerri
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Doria
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D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000375:Aging / Q000378:metabolism* / Q000502:physiology; D034961:Antigens, Nuclear; D002455:Cell Division; D002457:Cell Extracts; D002467:Cell Nucleus / Q000378:metabolism; D016207:Cytokines / Q000096:biosynthesis; D004247:DNA / Q000378:metabolism; D004265:DNA Helicases; D004268:DNA-Binding Proteins / Q000378:metabolism*; D019281:Dimerization; D006801:Humans; D000072200:Ku Autoantigen; D007963:Leukocytes, Mononuclear; D008938:Mitosis; D009687:Nuclear Proteins / Q000378:metabolism*
D034961:Antigens, Nuclear; D002457:Cell Extracts; D016207:Cytokines; D004268:DNA-Binding Proteins; D009687:Nuclear Proteins; D004247:DNA; D004265:DNA Helicases; C106893:XRCC5 protein, human; C000606509:Xrcc6 protein, human; D000072200:Ku Autoantigen