title: Age-associated alterations in inducible gene transcription in human CD4+ T lymphocytes.
abstract: Age associated immune dysregulation results in a pro-inflammatory state and increased susceptibility to infections and autoimmune diseases. Studies show that signaling initiated at the T cell antigen receptor (TCR) is impaired in CD4+ T cells from old compared to young mice. Here we examined TCR-inducible gene expression changes in CD4+ T cells during human aging. We reveal a dichotomy in gene expression mediated by the inducible transcription factor NF-κB. Most NF-κB target genes are not induced in a sustained manner in cells derived from older compared to younger individuals. However, a subset of NF-κB target genes including genes associated with chronic pro-inflammatory state in the elderly, such as interleukin 1 and 6, continue to be up-regulated even in the absence of NF-κB induction. In addition, we identify other widespread changes in gene expression between cells derived from older and younger individuals. Surprisingly, many of the most noteworthy age-associated changes in human CD4+ T cells differ from those seen in murine models. Our studies provide the first view of age-associated alteration of TCR-inducible gene expression in human CD4+ T cells.
authors: Laboratory of Molecular Biology and Immunology, National Institutes of Health, Baltimore, MD 21224, USA.
authors: Arsun
authors: A
authors: Bektas
authors: Yongqing
authors: Y
authors: Zhang
authors: William H
authors: WH
authors: Wood
authors: Kevin G
authors: KG
authors: Becker
authors: Karen
authors: K
authors: Madara
authors: Luigi
authors: L
authors: Ferrucci
authors: Ranjan
authors: R
authors: Sen
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000375:Aging / Q000276:immunology / Q000378:metabolism*; D015496:CD4-Positive T-Lymphocytes / Q000378:metabolism*; D005260:Female; D005786:Gene Expression Regulation; D006801:Humans; D015850:Interleukin-6 / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D016328:NF-kappa B / Q000378:metabolism*; D014158:Transcription, Genetic
chemical_list: C508600:IL6 protein, human; D015850:Interleukin-6; D016328:NF-kappa B
references: Int Immunopharmacol. 2004 Mar;4(3):327-47
references: 15037211
references: Gerontology. 1996;42(3):137-46
references: 8796372
references: Mutat Res. 1995 Feb;316(3):103-22
references: 7862174
references: Proc Natl Acad Sci U S A. 2005 Oct 25;102(43):15545-50
references: 16199517
references: Blood. 2005 Mar 15;105(6):2294-9
references: 15572589
references: Mol Cell Biol. 2000 Mar;20(6):2269-84
references: 10688673
references: Immunol Allergy Clin North Am. 2003 Feb;23(1):15-39
references: 12645876
references: Cell Res. 2011 Feb;21(2):223-44
references: 21243012
references: FASEB J. 2008 Jul;22(7):2142-50
references: 18267981
references: Mech Ageing Dev. 1996 Mar 29;86(3):173-95
references: 8733112
references: Mech Ageing Dev. 1998 May 15;102(2-3):149-63
references: 9720648
references: Annu Rev Med. 2000;51:245-70
references: 10774463
references: BMC Bioinformatics. 2005 Jun 08;6:144
references: 15941488
references: Aging Cell. 2011 Oct;10(5):853-67
references: 21711441
references: J Biol Chem. 1998 Dec 4;273(49):32833-41
references: 9830030
references: Immunity. 2005 Oct;23(4):445-58
references: 16226509
references: J Immunol. 2009 Apr 1;182(7):4175-82
references: 19299715
references: J Mol Diagn. 2003 May;5(2):73-81
references: 12707371
references: J Gerontol A Biol Sci Med Sci. 2010 May;65(5):532-7
references: 20045871
references: Curr Biol. 2002 Sep 17;12(18):1566-73
references: 12372248
references: J Immunol. 2006 Nov 1;177(9):6052-61
references: 17056531
references: Antioxid Redox Signal. 2001 Feb;3(1):147-56
references: 11291593
references: PLoS Biol. 2008 Dec 2;6(12):2853-68
references: 19053174
references: Cell Metab. 2011 Jan 5;13(1):11-22
references: 21195345
references: Nat Immunol. 2011 Jul 19;12(8):695-708
references: 21772278
references: ASN Neuro. 2009 May 05;1(2):
references: 19570030
references: Circ Res. 2007 Jun 8;100(11):1659-66
references: 17478731
references: Osteoarthritis Cartilage. 2009 Jan;17(1):43-8
references: 18571442
references: Biochem J. 1996 Sep 1;318 ( Pt 2):603-8
references: 8809053
references: J Immunol. 2009 Jan 15;182(2):1138-45
references: 19124757
references: J Immunol. 2001 Jun 15;166(12):7335-44
references: 11390484
references: Ageing Res Rev. 2011 Jul;10(3):370-8
references: 20933612
references: Int Immunol. 1997 Oct;9(10):1581-8
references: 9352364
references: Cell Cycle. 2008 Oct;7(19):2956-9
references: 18838863
references: Nature. 2004 Jun 24;429(6994):883-91
references: 15190254
references: J Immunol. 2003 Jan 15;170(2):895-904
references: 12517955
references: Immunol Rev. 2005 Jun;205:94-103
references: 15882347
references: Curr Biol. 2002 Apr 30;12(9):712-23
references: 12007414
references: J Clin Immunol. 2009 Jul;29(4):397-405
references: 19408108
references: Int Immunol. 2004 Dec;16(12):1711-21
references: 15492022
references: J Gerontol A Biol Sci Med Sci. 2003 Nov;58(11):975-83
references: 14630877
references: Mech Ageing Dev. 1992 Mar 15;63(1):57-68
references: 1376382
references: Mediators Inflamm. 2005 Aug 31;2005(4):245-7
references: 16192677
references: PLoS Biol. 2005 Sep;3(9):e274
references: 16048372
references: PLoS Biol. 2004 Dec;2(12):e427
references: 15562319
references: J Immunol. 2004 Dec 1;173(11):6719-26
references: 15557164
references: Nat Genet. 2004 Feb;36(2):197-204
references: 14730301
references: Am J Physiol Lung Cell Mol Physiol. 2000 Dec;279(6):L1005-28
references: 11076791