0 11 Age-related age-related JJ 12 21 decreases decrease NNS 22 24 in in IN 25 29 IL-2 il-2 NN 30 40 production production NN 41 43 by by IN 44 49 human human JJ 50 51 T t NN 52 57 cells cell NNS 58 61 are be VBP 62 72 associated associate VBN 73 77 with with IN 78 86 impaired impaired JJ 87 97 activation activation NN 98 100 of of IN 101 108 nuclear nuclear JJ 109 124 transcriptional transcriptional JJ 125 132 factors factor NNS 133 137 AP-1 ap-1 NN 138 141 and and CC 142 147 NF-AT NF-AT NNP 147 148 . . . 150 158 Although although IN 159 174 transcriptional transcriptional JJ 175 182 factors factor NNS 183 187 AP-1 ap-1 NN 188 191 and and CC 192 199 nuclear nuclear JJ 200 206 factor factor NN 207 209 of of IN 210 219 activated activate VBN 220 221 T t NN 222 227 cells cell NNS 228 229 ( ( ( 229 234 NF-AT NF-AT NNP 234 235 ) ) ) 236 239 are be VBP 240 249 important important JJ 250 253 for for IN 254 257 the the DT 258 264 normal normal JJ 265 274 induction induction NN 275 277 of of IN 278 282 IL-2 il-2 NN 282 283 , , , 284 286 it it PRP 287 289 is be VBZ 290 297 unknown unknown JJ 298 300 if if IN 301 304 the the DT 305 316 age-related age-related JJ 317 324 decline decline NN 325 327 in in IN 328 332 IL-2 il-2 NN 333 343 production production NN 344 346 by by IN 347 356 activated activate VBN 357 362 human human JJ 363 364 T t NN 365 370 cells cell NNS 371 374 may may MD 375 377 be be VB 378 388 associated associate VBN 389 393 with with IN 394 405 aberrancies aberrancy NNS 406 408 in in IN 409 424 transcriptional transcriptional JJ 425 435 regulatory regulatory JJ 436 444 proteins protein NNS 444 445 . . . 446 448 In in IN 449 452 the the DT 453 460 current current JJ 461 468 studies study NNS 468 469 , , , 470 474 IL-2 il-2 NN 475 485 production production NN 486 488 by by IN 489 490 T t NN 491 496 cells cell NNS 497 501 from from IN 502 509 elderly elderly JJ 510 511 ( ( ( 511 515 mean mean NN 516 518 78 78 CD 519 524 years year NNS 524 525 ) ) ) 526 529 and and CC 530 535 young young JJ 536 537 ( ( ( 537 541 mean mean NN 542 544 37 37 CD 545 550 years year NNS 550 551 ) ) ) 552 558 humans human NNS 559 562 was be VBD 563 571 measured measure VBN 572 574 in in IN 575 583 cultures culture NNS 584 594 stimulated stimulate VBN 595 599 with with IN 600 603 PHA PHA NNP 603 604 , , , 605 608 PHA PHA NNP 609 613 plus plus CC 614 617 PMA PMA NNP 617 618 , , , 619 630 crosslinked crosslinke VBN 631 639 anti-CD3 anti-cd3 JJ 640 643 mAB mAB NNP 644 648 OKT3 OKT3 NNP 649 653 plus plus CC 654 657 PMA PMA NNP 657 658 , , , 659 661 or or CC 662 665 PMA PMA NNP 666 670 plus plus CC 671 680 ionomycin ionomycin NN 680 681 . . . 682 693 Substantial substantial JJ 694 703 decreases decrease NNS 704 706 of of IN 707 711 IL-2 il-2 NN 712 722 production production NN 723 727 were be VBD 728 736 observed observe VBN 737 740 for for IN 741 745 cell cell NN 746 754 cultures culture NNS 755 759 from from IN 760 761 7 7 CD 762 764 of of IN 765 767 12 12 CD 768 775 elderly elderly JJ 776 787 individuals individual NNS 788 790 in in IN 791 799 response response NN 800 802 to to TO 803 806 the the DT 807 816 different different JJ 817 824 stimuli stimulus NNS 824 825 , , , 826 833 whereas whereas IN 834 837 the the DT 838 844 levels level NNS 845 847 of of IN 848 852 IL-2 il-2 NN 853 861 produced produce VBN 862 864 by by IN 865 875 stimulated stimulate VBN 876 877 T t NN 878 883 cells cell NNS 884 888 from from IN 889 894 other other JJ 895 902 elderly elderly JJ 903 914 individuals individual NNS 915 919 were be VBD 920 930 equivalent equivalent JJ 931 933 to to TO 934 939 those those DT 940 948 observed observe VBN 949 952 for for IN 953 963 stimulated stimulate VBN 964 965 T t NN 966 971 cells cell NNS 972 974 of of IN 975 980 young young JJ 981 989 subjects subject NNS 989 990 . . . 991 999 Analyses analysis NNS 1000 1002 of of IN 1003 1010 nuclear nuclear JJ 1011 1019 extracts extract NNS 1020 1022 by by IN 1023 1038 electrophoretic electrophoretic JJ 1039 1042 DNA dna NN 1043 1051 mobility mobility NN 1052 1057 shift shift NN 1058 1064 assays assay NNS 1065 1071 showed show VBD 1072 1076 that that IN 1077 1086 decreased decrease VBN 1087 1091 IL-2 il-2 NN 1092 1102 production production NN 1103 1105 by by IN 1106 1116 stimulated stimulate VBN 1117 1118 T t NN 1119 1124 cells cell NNS 1125 1127 of of IN 1128 1135 elderly elderly JJ 1136 1147 individuals individual NNS 1148 1151 was be VBD 1152 1159 closely closely RB 1160 1170 associated associate VBN 1171 1175 with with IN 1176 1187 impairments impairment NNS 1188 1190 in in IN 1191 1194 the the DT 1195 1205 activation activation NN 1206 1208 of of IN 1209 1213 both both CC 1214 1218 AP-1 ap-1 NN 1219 1222 and and CC 1223 1228 NF-AT NF-AT NNP 1228 1229 . . . 1230 1232 By by IN 1233 1241 contrast contrast NN 1241 1242 , , , 1243 1244 T t NN 1245 1250 cells cell NNS 1251 1255 from from IN 1256 1263 elderly elderly JJ 1264 1272 subjects subject NNS 1273 1277 with with IN 1278 1284 normal normal JJ 1285 1291 levels level NNS 1292 1294 of of IN 1295 1299 IL-2 il-2 NN 1300 1310 production production NN 1311 1320 exhibited exhibit VBD 1321 1327 normal normal JJ 1328 1338 activation activation NN 1339 1341 of of IN 1342 1346 AP-1 ap-1 NN 1347 1350 and and CC 1351 1356 NF-AT NF-AT NNP 1356 1357 . . . 1358 1360 In in IN 1361 1369 addition addition NN 1369 1370 , , , 1371 1374 the the DT 1375 1382 results result NNS 1383 1385 of of IN 1386 1397 competition competition NN 1398 1409 experiments experiment NNS 1410 1419 analyzing analyze VBG 1420 1423 the the DT 1424 1430 normal normal JJ 1431 1441 components component NNS 1442 1444 of of IN 1445 1450 NF-AT NF-AT NNP 1451 1457 showed show VBD 1458 1462 that that IN 1463 1466 the the DT 1467 1478 age-related age-related JJ 1479 1489 reductions reduction NNS 1490 1492 in in IN 1493 1511 stimulus-dependent stimulus-dependent JJ 1512 1517 NF-AT NF-AT NNP 1518 1527 complexes complex NNS 1528 1540 corresponded correspond VBD 1541 1543 to to TO 1544 1547 the the DT 1548 1552 slow slow JJ 1553 1562 migrating migrate VBG 1563 1572 complexes complex NNS 1573 1577 that that WDT 1578 1582 were be VBD 1583 1591 composed compose VBN 1592 1594 of of IN 1595 1606 c-Fos/c-Jun c-fos/c-jun NN 1607 1611 AP-1 ap-1 NN 1611 1612 . . . 1613 1616 The the DT 1617 1624 resting resting NN 1625 1628 and and CC 1629 1639 stimulated stimulate VBN 1640 1646 levels level NNS 1647 1649 of of IN 1650 1652 NF NF NNP 1653 1658 kappa kappa NN 1659 1660 B B NNP 1661 1665 were be VBD 1666 1673 reduced reduce VBN 1674 1676 in in IN 1677 1678 T t NN 1679 1684 cells cell NNS 1685 1689 from from IN 1690 1697 certain certain JJ 1698 1705 elderly elderly JJ 1706 1717 individuals individual NNS 1717 1718 ; ; : 1719 1726 however however RB 1726 1727 , , , 1728 1739 alterations alteration NNS 1740 1742 of of IN 1743 1745 NF NF NNP 1746 1751 kappa kappa NN 1752 1753 B B NNP 1754 1757 did do VBD 1758 1761 not not RB 1762 1771 correlate correlate VB 1772 1776 with with IN 1777 1784 changes change NNS 1785 1787 in in IN 1788 1792 IL-2 il-2 NN 1793 1803 expression expression NN 1803 1804 . . . 1805 1809 Thus thus RB 1809 1810 , , , 1811 1816 these these DT 1817 1824 results result NNS 1825 1829 show show VBP 1830 1834 that that IN 1835 1846 age-related age-related JJ 1847 1858 impairments impairment NNS 1859 1861 in in IN 1862 1865 the the DT 1866 1876 activation activation NN 1877 1879 of of IN 1880 1884 AP-1 ap-1 NN 1885 1888 and and CC 1889 1894 NF-AT NF-AT NNP 1895 1898 are be VBP 1899 1906 closely closely RB 1907 1917 associated associate VBN 1918 1922 with with IN 1923 1932 decreased decrease VBN 1933 1943 expression expression NN 1944 1946 of of IN 1947 1951 IL-2 il-2 NN 1952 1955 and and CC 1956 1963 further further RB 1964 1971 suggest suggest VBP 1972 1976 that that IN 1977 1988 aberrancies aberrancy NNS 1989 1991 in in IN 1992 1995 the the DT 1996 2005 signaling signaling NN 2006 2014 pathways pathway NNS 2015 2024 important important JJ 2025 2028 for for IN 2029 2032 the the DT 2033 2042 induction induction NN 2043 2045 of of IN 2046 2063 transcriptionally transcriptionally RB 2064 2070 active active JJ 2071 2082 c-Fos/c-Jun c-fos/c-jun NN 2083 2087 AP-1 ap-1 NN 2088 2091 may may MD 2092 2102 contribute contribute VB 2103 2105 to to TO 2106 2109 the the DT 2110 2118 impaired impaired JJ 2119 2129 activation activation NN 2130 2132 of of IN 2133 2138 NF-AT NF-AT NNP 2138 2139 . . .