CELL-PROLIFERATION AND KU PROTEIN EXPRESSION IN AGING HUMANS

Previous studies on DNA repair in ageing have demonstrated increased f requencies of single and double strand breaks in lymphocytes from elde rly subjects and, as a consequence, decreased efficiency in DNA replic ation. We have investigated the relationship between cell proliferatio n and the nuclear expression of ku protein in a human population of 43 subjects of different ages. Ku is an heterodimeric protein composed o f 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 an d the production of Th1- and Th2-type cytokines. Moreover, nuclear ext racts were obtained from activated lymphocytes to evaluate by a gel re tardation assay the presence and the functional activity of the hetero dimer ku 70/80. Our results indicate that ageing affects the mitotic r esponsiveness and cytokine production to a significant extent, but onl y marginally the expression of ku 70/80. These findings suggest that t he age-related impairment in DNA repair mechanisms are only in part re lated to the reduced expression of ku protein able to recognize DNA da mage. (C) 1998 Published by Elsevier Science Ireland Ltd.