0 8 Impaired impaired JJ 9 18 induction induction NN 19 21 of of IN 22 33 c-fos/c-jun c-fos/c-jun NN 34 39 genes gene NNS 40 43 and and CC 44 46 of of IN 47 62 transcriptional transcriptional JJ 63 73 regulatory regulatory JJ 74 82 proteins protein NNS 83 90 binding bind VBG 91 99 distinct distinct JJ 100 111 c-fos/c-jun c-fos/c-jun NN 112 120 promoter promoter NN 121 129 elements element NNS 130 132 in in IN 133 142 activated activate VBN 143 148 human human JJ 149 150 T t NN 151 156 cells cell NNS 157 163 during during IN 164 169 aging aging NN 169 170 . . . 172 175 The the DT 176 186 activation activation NN 187 189 of of IN 190 205 transcriptional transcriptional JJ 206 212 factor factor NN 213 224 c-Fos/c-Jun c-fos/c-jun NN 225 229 AP-1 ap-1 NN 230 232 is be VBZ 233 242 essential essential JJ 243 246 for for IN 247 253 normal normal JJ 254 255 T t NN 256 260 cell cell NN 261 275 responsiveness responsiveness NN 276 279 and and CC 280 282 is be VBZ 283 288 often often RB 289 297 impaired impaired JJ 298 300 in in IN 301 302 T t NN 303 308 cells cell NNS 309 315 during during IN 316 321 aging aging NN 321 322 . . . 323 325 In in IN 326 329 the the DT 330 337 present present JJ 338 343 study study NN 343 344 , , , 345 347 we we PRP 348 360 investigated investigate VBD 361 368 whether whether IN 369 380 aberrancies aberrancy NNS 381 383 in in IN 384 387 the the DT 388 398 regulation regulation NN 399 401 of of IN 402 413 c-fos/c-jun c-fos/c-jun NN 414 416 at at IN 417 420 the the DT 421 425 mRNA mrna NN 426 428 or or CC 429 436 protein protein NN 437 442 level level NN 443 448 might might MD 449 457 underlie underlie VB 458 461 the the DT 462 476 age-associated age-associated JJ 477 488 impairments impairment NNS 489 491 of of IN 492 496 AP-1 ap-1 NN 497 499 in in IN 500 505 human human JJ 506 507 T t NN 508 513 cells cell NNS 513 514 . . . 515 522 Whereas whereas IN 523 524 T t NN 525 530 cells cell NNS 531 535 from from IN 536 541 young young JJ 542 550 subjects subject NNS 551 561 stimulated stimulate VBN 562 566 with with IN 567 579 cross-linked cross-linked JJ 580 595 anti-CD3epsilon anti-cd3epsilon JJ 596 599 mAb mab NN 600 604 OKT3 OKT3 NNP 605 609 plus plus CC 610 613 PMA PMA NNP 614 616 or or CC 617 621 with with IN 622 625 the the DT 626 632 lectin lectin NN 633 636 PHA PHA NNP 637 641 plus plus CC 642 645 PMA PMA NNP 646 658 demonstrated demonstrate VBD 659 671 considerable considerable JJ 672 681 increases increase NNS 682 684 in in IN 685 690 c-Fos c-fos NN 691 698 protein protein NN 699 709 expression expression NN 709 710 , , , 711 714 the the DT 715 725 expression expression NN 726 728 of of IN 729 734 c-Fos c-fos NN 735 738 but but CC 739 742 not not RB 743 748 c-Jun c-jun NN 749 752 was be VBD 753 761 markedly markedly RB 762 769 reduced reduce VBN 770 772 in in IN 773 783 stimulated stimulate VBN 784 785 T t NN 786 791 cells cell NNS 792 796 from from IN 797 804 certain certain JJ 805 812 elderly elderly JJ 813 821 subjects subject NNS 821 822 . . . 823 825 In in IN 826 834 addition addition NN 834 835 , , , 836 841 RNase RNase NNP 842 852 protection protection NN 853 859 assays assay NNS 860 868 revealed reveal VBD 869 873 that that IN 874 897 anti-CD3/PMA-stimulated anti-cd3/pma-stimulated JJ 898 899 T t NN 900 905 cells cell NNS 906 910 from from IN 911 912 a a DT 913 924 substantial substantial JJ 925 935 proportion proportion NN 936 938 of of IN 939 946 elderly elderly JJ 947 955 subjects subject NNS 956 965 exhibited exhibit VBD 966 975 decreased decrease VBN 976 982 levels level NNS 983 985 of of IN 986 991 c-fos c-fos NN 992 998 and/or and/or CC 999 1004 c-jun c-jun NN 1005 1009 mRNA mrna NN 1010 1018 compared compare VBN 1019 1021 to to TO 1022 1023 T t NN 1024 1029 cells cell NNS 1030 1034 from from IN 1035 1040 young young JJ 1041 1049 subjects subject NNS 1049 1050 . . . 1051 1056 Using use VBG 1057 1072 electrophoretic electrophoretic JJ 1073 1081 mobility mobility NN 1082 1087 shift shift NN 1088 1094 assays assay NNS 1094 1095 , , , 1096 1099 the the DT 1100 1106 levels level NNS 1107 1109 of of IN 1110 1117 nuclear nuclear JJ 1118 1128 regulatory regulatory JJ 1129 1137 proteins protein NNS 1138 1149 recognizing recognize VBG 1150 1153 the the DT 1154 1158 AP-1 ap-1 NN 1159 1168 consensus consensus NN 1169 1172 TRE tre NN 1173 1178 motif motif NN 1178 1179 , , , 1180 1183 the the DT 1184 1192 proximal proximal JJ 1193 1198 c-jun c-jun NN 1199 1207 TRE-like tre-like JJ 1208 1216 promoter promoter NN 1217 1224 element element NN 1224 1225 , , , 1226 1229 and and CC 1230 1233 the the DT 1234 1239 c-fos c-fos NN 1240 1245 serum serum NN 1246 1254 response response NN 1255 1262 element element NN 1263 1264 ( ( ( 1264 1267 SRE SRE NNP 1267 1268 ) ) ) 1269 1273 were be VBD 1274 1284 determined determine VBN 1285 1287 in in IN 1288 1295 resting rest VBG 1296 1299 and and CC 1300 1310 stimulated stimulate VBN 1311 1312 T t NN 1313 1318 cells cell NNS 1318 1319 . . . 1320 1328 Although although IN 1329 1332 the the DT 1333 1344 stimulation stimulation NN 1345 1347 of of IN 1348 1349 T t NN 1350 1355 cells cell NNS 1356 1360 from from IN 1361 1366 young young JJ 1367 1375 subjects subject NNS 1376 1384 resulted result VBD 1385 1387 in in IN 1388 1399 coordinated coordinate VBN 1400 1409 increases increase NNS 1410 1412 of of IN 1413 1420 nuclear nuclear JJ 1421 1428 protein protein NN 1429 1438 complexes complex NNS 1439 1446 binding bind VBG 1447 1450 the the DT 1451 1455 AP-1 ap-1 NN 1456 1459 TRE tre NN 1459 1460 , , , 1461 1466 c-jun c-jun NN 1467 1470 TRE tre NN 1470 1471 , , , 1472 1475 and and CC 1476 1481 c-fos c-fos NN 1482 1485 SRE SRE NNP 1486 1489 DNA DNA NNP 1490 1498 sequence sequence NN 1499 1505 motifs motif NNS 1505 1506 , , , 1507 1518 age-related age-related JJ 1519 1529 reductions reduction NNS 1530 1532 in in IN 1533 1536 the the DT 1537 1547 activation activation NN 1548 1550 of of IN 1551 1555 AP-1 ap-1 NN 1556 1560 were be VBD 1561 1572 accompanied accompany VBN 1573 1575 by by IN 1576 1585 decreased decrease VBN 1586 1592 levels level NNS 1593 1595 of of IN 1596 1601 c-jun c-jun NN 1602 1605 TRE tre NN 1606 1609 and and CC 1610 1615 c-fos c-fos NN 1616 1619 SRE sre NN 1620 1627 binding binding NN 1628 1637 complexes complex NNS 1637 1638 . . . 1639 1650 Furthermore furthermore RB 1650 1651 , , , 1652 1655 the the DT 1656 1663 nuclear nuclear JJ 1664 1671 protein protein NN 1672 1681 complexes complex NNS 1682 1689 binding bind VBG 1690 1693 the the DT 1694 1697 SRE SRE NNP 1698 1703 motif motif NN 1704 1711 induced induce VBN 1712 1714 in in IN 1715 1724 activated activate VBN 1725 1726 T t NN 1727 1732 cells cell NNS 1733 1735 of of IN 1736 1741 young young JJ 1742 1745 and and CC 1746 1753 elderly elderly JJ 1754 1762 subjects subject NNS 1763 1772 contained contain VBD 1773 1778 serum serum NN 1779 1787 response response NN 1788 1794 factor factor NN 1795 1798 and and CC 1799 1804 Elk-1 elk-1 NN 1805 1813 pointing pointing NN 1814 1820 toward toward IN 1821 1832 age-related age-related JJ 1833 1840 defects defect NNS 1841 1843 in in IN 1844 1847 the the DT 1848 1858 activation activation NN 1859 1861 of of IN 1862 1877 transcriptional transcriptional JJ 1878 1888 regulatory regulatory JJ 1889 1897 proteins protein NNS 1898 1906 distinct distinct JJ 1907 1911 from from IN 1912 1922 c-jun/AP-1 c-jun/ap-1 NN 1922 1923 . . . 1924 1929 These these DT 1930 1937 results result NNS 1938 1945 suggest suggest VBP 1946 1950 that that IN 1951 1961 underlying underlie VBG 1962 1973 aberrancies aberrancy NNS 1974 1976 in in IN 1977 1980 the the DT 1981 1990 induction induction NN 1991 1993 of of IN 1994 2005 c-fos/c-jun c-fos/c-jun NN 2006 2008 as as RB 2009 2013 well well RB 2014 2016 as as IN 2017 2022 their their PRP$ 2023 2030 nuclear nuclear JJ 2031 2041 regulatory regulatory JJ 2042 2050 proteins protein NNS 2051 2054 may may MD 2055 2065 contribute contribute VB 2066 2068 to to TO 2069 2072 the the DT 2073 2084 age-related age-related JJ 2085 2096 impairments impairment NNS 2097 2099 of of IN 2100 2104 AP-1 ap-1 NN 2105 2115 activation activation NN 2116 2118 in in IN 2119 2124 human human JJ 2125 2126 T t NN 2127 2132 cells cell NNS 2132 2133 . . .