0 9 Decreased decrease VBN 10 29 proteasome-mediated proteasome-mediated JJ 30 41 degradation degradation NN 42 44 in in IN 45 46 T t NN 47 52 cells cell NNS 53 57 from from IN 58 61 the the DT 62 69 elderly elderly JJ 69 70 : : : 71 72 A a DT 73 77 role role NN 78 80 in in IN 81 87 immune immune JJ 88 98 senescence senescence NN 98 99 . . . 101 110 Induction Induction NNP 111 113 of of IN 114 122 NFkappaB NFkappaB NNP 123 125 is be VBZ 126 127 a a DT 128 134 highly highly RB 135 144 regulated regulate VBN 145 152 process process NN 153 162 requiring require VBG 163 178 phosphorylation phosphorylation NN 178 179 , , , 180 194 ubiquitination ubiquitination NN 194 195 , , , 196 199 and and CC 200 219 proteasome-mediated proteasome-mediated JJ 220 231 degradation degradation NN 232 234 of of IN 235 238 the the DT 239 248 cytosolic cytosolic JJ 249 258 inhibitor inhibitor NN 259 271 IkappaBalpha IkappaBalpha NNP 271 272 . . . 273 281 Analyses analysis NNS 282 284 of of IN 285 288 the the DT 289 299 regulation regulation NN 300 302 of of IN 303 315 IkappaBalpha IkappaBalpha NNP 316 318 in in IN 319 336 TNF-alpha-treated tnf-alpha-treated JJ 337 338 T t NN 339 350 lymphocytes lymphocyte NNS 351 355 from from IN 356 361 young young JJ 362 365 and and CC 366 373 elderly elderly JJ 374 380 donors donor NNS 381 389 revealed reveal VBD 390 398 severely severely RB 399 410 compromised compromise VBN 411 422 degradation degradation NN 423 425 of of IN 426 438 IkappaBalpha IkappaBalpha NNP 439 441 in in IN 442 443 T t NN 444 449 cells cell NNS 450 454 from from IN 455 458 the the DT 459 466 elderly elderly JJ 466 467 . . . 468 479 Examination Examination NNP 480 482 of of IN 483 501 activation-induced activation-induced JJ 502 517 phosphorylation phosphorylation NN 518 521 and and CC 522 536 ubiquitination ubiquitination NN 537 539 of of IN 540 552 IkappaBalpha IkappaBalpha NNP 553 556 did do VBD 557 560 not not RB 561 572 demonstrate demonstrate VB 573 576 any any DT 577 588 significant significant JJ 589 600 age-related age-related JJ 601 612 alterations alteration NNS 612 613 . . . 614 621 However however RB 621 622 , , , 623 634 examination examination NN 635 637 of of IN 638 648 proteasome proteasome NN 649 657 activity activity NN 658 660 in in IN 661 666 these these DT 667 668 T t NN 669 674 cells cell NNS 675 680 using use VBG 681 692 fluorogenic fluorogenic JJ 693 700 peptide peptide NN 701 707 assays assay NNS 708 716 revealed reveal VBD 717 718 a a DT 719 730 significant significant JJ 731 742 age-related age-related JJ 743 750 decline decline NN 751 753 in in IN 754 766 chymotryptic chymotryptic JJ 767 775 activity activity NN 775 776 . . . 777 782 These these DT 783 790 results result NNS 791 798 suggest suggest VBP 799 803 that that IN 804 805 a a DT 806 813 decline decline NN 814 816 in in IN 817 827 proteasome proteasome NN 828 836 activity activity NN 837 844 results result VBZ 845 847 in in IN 848 849 a a DT 850 857 failure failure NN 858 860 to to TO 861 866 fully fully RB 867 874 degrade degrade VB 875 887 IkappaBalpha IkappaBalpha NNP 888 890 in in IN 891 894 the the DT 895 902 elderly elderly JJ 902 903 . . . 904 908 This this DT 909 916 failure failure NN 917 919 to to TO 920 927 degrade degrade VB 928 940 IkappaBalpha IkappaBalpha NNP 941 944 may may MD 945 953 underlie underlie VB 954 958 both both CC 959 962 the the DT 963 971 observed observe VBN 972 980 decrease decrease NN 981 983 in in IN 984 992 NFkappaB NFkappaB NNP 993 1002 induction induction NN 1003 1006 and and CC 1007 1010 the the DT 1011 1015 IL-2 il-2 NN 1016 1024 receptor receptor NN 1025 1035 expression expression NN 1036 1038 in in IN 1039 1050 TNF-treated tnf-treated JJ 1051 1052 T t NN 1053 1058 cells cell NNS 1059 1065 during during IN 1066 1071 aging aging NN 1071 1072 . . . 1073 1077 Thus thus RB 1077 1078 , , , 1079 1088 decreased decrease VBD 1089 1108 proteasome-mediated proteasome-mediated JJ 1109 1120 degradation degradation NN 1121 1124 may may MD 1125 1127 be be VB 1128 1135 central central JJ 1136 1138 to to TO 1139 1145 immune immune JJ 1146 1157 dysfunction dysfunction NN 1158 1162 that that WDT 1163 1174 accompanies accompany VBZ 1175 1180 aging aging NN 1180 1181 . . . 1182 1191 Copyright Copyright NNP 1192 1196 1999 1999 CD 1197 1205 Academic Academic NNP 1206 1211 Press Press NNP 1211 1212 . . .