title: Thymic function failure and C-reactive protein levels are independent predictors of all-cause mortality in healthy elderly humans.
abstract: Relationship between thymic function and elderly survival has been suspected, despite the fact that formal proof is elusive due to technical limitations of thymic function-related markers. The newly described sj/β-TREC ratio allows now, by overcoming these limitations, an accurate measurement of thymic output in elderly humans. Thus, the aim of this study was to determine the impact of thymic function and inflammatory markers on healthy elderly human survival. Healthy volunteers (n = 151), aged over 65, were asked to participate (CARRERITAS cohort). Subjects were excluded if diagnosed of dementia or, during the last 6 months, had clinical data of infection, hospital admission, antitumor therapy, or any treatment that could influence the immune status. Thymic function (sj/β-TREC ratio), CD4:CD8 T cell ratio, C-reactive protein, interleukin-6, and neutrophilia were determined from basal samples. All basal variables and age were associated with 2-year all-cause mortality. Multivariate analysis showed that only thymic function and C-reactive protein were independently associated with time to death. In conclusion, we show, for the first time, the direct role of thymic function in human survival. C-reactive protein raise is also a marker of mortality in the healthy elderly, in a thymic-independent way.
authors.affiliation: Laboratory of Molecular Immuno-Biology, Hospital General Universitario Gregorio Marañón, Madrid, Spain. s.ferrandomartinez@gmail.com
authors.forename: Sara
authors.initials: S
authors.lastname: Ferrando-Martínez
authors.forename: María Concepción
authors.initials: MC
authors.lastname: Romero-Sánchez
authors.forename: Rafael
authors.initials: R
authors.lastname: Solana
authors.forename: Juan
authors.initials: J
authors.lastname: Delgado
authors.forename: Rafael
authors.initials: R
authors.lastname: de la Rosa
authors.forename: Ma Angeles
authors.initials: MA
authors.lastname: Muñoz-Fernández
authors.forename: Ezequiel
authors.initials: E
authors.lastname: Ruiz-Mateos
authors.forename: Manuel
authors.initials: M
authors.lastname: Leal
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000375:Aging / Q000097:blood*; D015415:Biomarkers / Q000097:blood; D002097:C-Reactive Protein / Q000378:metabolism*; D002423:Cause of Death / Q000639:trends; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008297:Male; D011379:Prognosis; D012016:Reference Values; D012189:Retrospective Studies; D013030:Spain / Q000453:epidemiology; D013950:Thymus Gland / Q000378:metabolism* / Q000473:pathology*
chemical_list: D015415:Biomarkers; D002097:C-Reactive Protein
references.citation: Exp Gerontol. 2008 Feb;43(2):61-5
references.pmid: 17870272
references.citation: AIDS Rev. 2010 Oct-Dec;12(4):218-30
references.pmid: 21179186
references.citation: Maturitas. 2011 Apr;68(4):322-30
references.pmid: 21316879
references.citation: PLoS One. 2011 Feb 17;6(2):e16103
references.pmid: 21379581
references.citation: Clin Infect Dis. 2000 Jun;30(6):931-3
references.pmid: 10880303
references.citation: Nat Med. 2000 Sep;6(9):1036-42
references.pmid: 10973325
references.citation: Virulence. 2010 Jul-Aug;1(4):295-8
references.pmid: 21178458
references.citation: Biogerontology. 2008 Oct;9(5):299-308
references.pmid: 18369735
references.citation: Rejuvenation Res. 2010 Apr-Jun;13(2-3):288-91
references.pmid: 19954334
references.citation: Clin Infect Dis. 2008 Apr 1;46(7):1078-84
references.pmid: 18444828
references.citation: J Gerontol A Biol Sci Med Sci. 1995 Nov;50(6):B378-82
references.pmid: 7583794
references.citation: Clin Immunol. 2008 Apr;127(1):107-18
references.pmid: 18222733
references.citation: Ann N Y Acad Sci. 2000 Jun;908:244-54
references.pmid: 10911963
references.citation: Immunity. 2004 Dec;21(6):757-68
references.pmid: 15589165
references.citation: AIDS. 2011 Sep 24;25(15):1813-22
references.pmid: 21412126
references.citation: Am J Cardiol. 2003 Sep 1;92(5):522-8
references.pmid: 12943870
references.citation: Biogerontology. 2006 Oct-Dec;7(5-6):471-81
references.pmid: 16957868
references.citation: FASEB J. 2003 Jun;17(9):1183-5
references.pmid: 12709402
references.citation: Age (Dordr). 2009 Jun;31(2):87-97
references.pmid: 19507053
references.citation: Circulation. 2010 Nov 2;122(18):1837-45
references.pmid: 20956207
references.citation: Rev Esp Salud Publica. 2001 Jan-Feb;75(1):55-62
references.pmid: 11400415
references.citation: Age (Dordr). 2011 Jun;33(2):197-207
references.pmid: 20700658
references.citation: Exp Gerontol. 2007 Aug;42(8):753-61
references.pmid: 17606347
references.citation: Immunol Rev. 2005 Jun;205:257-68
references.pmid: 15882359
references.citation: Nat Immunol. 2004 Feb;5(2):133-9
references.pmid: 14749784
references.citation: Age (Dordr). 2011 Jun;33(2):209-17
references.pmid: 20617391
references.citation: J Immunol Methods. 2010 Jan 31;352(1-2):111-7
references.pmid: 19919841
references.citation: J Pathol Bacteriol. 1967 Apr;93(2):661-71
references.pmid: 6069627
references.citation: Clin Immunol. 2005 May;115(2):138-46
references.pmid: 15885636
references.citation: Crit Rev Oncol Hematol. 2007 Nov;64(2):90-105
references.pmid: 17446082
references.citation: Mech Ageing Dev. 1998 May 15;102(2-3):187-98
references.pmid: 9720651
references.citation: Blood. 2002 May 15;99(10):3702-6
references.pmid: 11986226
references.citation: Vaccine. 2005 May 9;23(25):3232-5
references.pmid: 15837226
references.citation: J Antimicrob Chemother. 2009 Sep;64(3):579-88
references.pmid: 19608579
references.citation: Curr Opin Immunol. 2010 Aug;22(4):507-13
references.pmid: 20667703
references.citation: Immunology. 2007 Apr;120(4):435-46
references.pmid: 17313487