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How the Aging Process Affects Our Immune System: Mechanisms, Consequences, and Perspectives for Intervention

  • Dietmar Herndler-BrandstetterEmail author
Chapter
Part of the International Perspectives on Aging book series (Int. Perspect. Aging, volume 10)

Abstract

The aging of the immune system involves a complex set of changes that is collectively referred to as immune senescence. Clinically, immune senescence has been associated with decreased protection following vaccinations, increased morbidity and mortality from infectious diseases, increased risk of cancer, and increased incidence of autoimmune and inflammatory diseases. Although our understanding of the mechanisms that drive immune senescence has improved during the past decades, we are still far away from therapies that would be able to delay or even prevent the development of immune senescence in humans. This book chapter will illustrate our current knowledge of how the aging process affects our immune system, which key factors are responsible for the aging of immune cells, how environmental factors such as certain life-long viral infections may affect immunological aging, and what challenges the scientific community has to overcome to successfully implement strategies that delay or prevent immunosenescence and thereby increase the human health span.

Keywords

Infective Endocarditis Herpes Zoster Varicella Zoster Virus Influenza Vaccination Somatic Stem Cell 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

Notes

Acknowledgment 

Dietmar Herndler-Brandstetter is an Erwin Schrodinger Fellow (funded by the Austrian Science Fund, J3220-B19, 2012–2013) and a previous FLARE Fellow (funded by the Austrian Federal Ministry of Science and Research, 2008–2011).

References

  1. Agius E, Lacy KE, Vukmanovic-Stejic M, Jagger AL, Papageorgiou AP, Hall S, Reed JR, Curnow SJ, Fuentes-Duculan J, Buckley CD, Salmon M, Taams LS, Krueger J, Greenwood J, Klein N, Rustin MH, Akbar AN (2009) Decreased TNF-alpha synthesis by macrophages restricts cutaneous immunosurveillance by memory CD4+ T cells during aging. J Exp Med 206(9):1929–1940. doi: 10.1084/jem.20090896 CrossRefGoogle Scholar
  2. Almanzar G, Schwaiger S, Jenewein B, Keller M, Herndler-Brandstetter D, Wurzner R, Schonitzer D, Grubeck-Loebenstein B (2005) Long-term cytomegalovirus infection leads to significant changes in the composition of the CD8+ T-cell repertoire, which may be the basis for an imbalance in the cytokine production profile in elderly persons. J Virol 79(6):3675–3683CrossRefGoogle Scholar
  3. Alves NL, van Leeuwen EM, Remmerswaal EB, Vrisekoop N, Tesselaar K, Roosnek E, ten Berge IJ, van Lier RA (2007) A new subset of human naive CD8+ T cells defined by low expression of IL-7R alpha. J Immunol 179(1):221–228CrossRefGoogle Scholar
  4. Aspinall R, Mitchell W (2008) Reversal of age-associated thymic atrophy: treatments, delivery, and side effects. Exp Gerontol 43(7):700–705CrossRefGoogle Scholar
  5. Aspinall R, Pido-Lopez J, Imami N, Henson SM, Ngom PT, Morre M, Niphuis H, Remarque E, Rosenwirth B, Heeney JL (2007) Old rhesus macaques treated with interleukin-7 show increased TREC levels and respond well to influenza vaccination. Rejuvenation Res 10(1):5–17CrossRefGoogle Scholar
  6. Aydar Y, Balogh P, Tew JG, Szakal AK (2002) Age-related depression of FDC accessory functions and CD21 ligand-mediated repair of co-stimulation. Eur J Immunol 32(10):2817–2826CrossRefGoogle Scholar
  7. Bouchlaka MN, Sckisel GD, Chen M, Mirsoian A, Zamora AE, Maverakis E, Wilkins DE, Alderson KL, Hsiao HH, Weiss JM, Monjazeb AM, Hesdorffer C, Ferrucci L, Longo DL, Blazar BR, Wiltrout RH, Redelman D, Taub DD, Murphy WJ (2013) Aging predisposes to acute inflammatory induced pathology after tumor immunotherapy. J Exp Med 210(11):2223–2237. doi: 10.1084/jem.20131219 CrossRefGoogle Scholar
  8. Brenchley JM, Karandikar NJ, Betts MR, Ambrozak DR, Hill BJ, Crotty LE, Casazza JP, Kuruppu J, Migueles SA, Connors M, Roederer M, Douek DC, Koup RA (2003) Expression of CD57 defines replicative senescence and antigen-induced apoptotic death of CD8+ T cells. Blood 101(7):2711–2720CrossRefGoogle Scholar
  9. Brunner S, Herndler-Brandstetter D, Arnold CR, Wiegers GJ, Villunger A, Hackl M, Grillari J, Moreno-Villanueva M, Burkle A, Grubeck-Loebenstein B (2012) Upregulation of miR-24 is associated with a decreased DNA damage response upon etoposide treatment in highly differentiated CD8(+) T cells sensitizing them to apoptotic cell death. Aging Cell 11(4):579–587. doi: 10.1111/j.1474-9726.2012.00819.x CrossRefGoogle Scholar
  10. Chen WH, Kozlovsky BF, Effros RB, Grubeck-Loebenstein B, Edelman R, Sztein MB (2009) Vaccination in the elderly: an immunological perspective. Trends Immunol 30(7):351–359CrossRefGoogle Scholar
  11. Chiu WK, Fann M, Weng NP (2006) Generation and growth of CD28nullCD8+ memory T cells mediated by IL-15 and its induced cytokines. J Immunol 177(11):7802–7810CrossRefGoogle Scholar
  12. Cicin-Sain L, Sylwester AW, Hagen SI, Siess DC, Currier N, Legasse AW, Fischer MB, Koudelka CW, Axthelm MK, Nikolich-Zugich J, Picker LJ (2011) Cytomegalovirus-specific T cell immunity is maintained in immunosenescent rhesus macaques. J Immunol 187(4):1722–1732. doi: 10.4049/jimmunol.1100560 CrossRefGoogle Scholar
  13. Colonna-Romano G, Bulati M, Aquino A, Scialabba G, Candore G, Lio D, Motta M, Malaguarnera M, Caruso C (2003) B cells in the aged: CD27, CD5, and CD40 expression. Mech Ageing Dev 124(4):389–393CrossRefGoogle Scholar
  14. Di Rosa F, Pabst R (2005) The bone marrow: a nest for migratory memory T cells. Trends Immunol 26(7):360–366CrossRefGoogle Scholar
  15. Dixit VD, Yang H, Sun Y, Weeraratna AT, Youm YH, Smith RG, Taub DD (2007) Ghrelin promotes thymopoiesis during aging. J Clin Invest 117(10):2778–2790CrossRefGoogle Scholar
  16. Effros RB, Cai Z, Linton PJ (2003) CD8 T cells and aging. Crit Rev Immunol 23(1–2):45–64CrossRefGoogle Scholar
  17. Fagnoni FF, Vescovini R, Passeri G, Bologna G, Pedrazzoni M, Lavagetto G, Casti A, Franceschi C, Passeri M, Sansoni P (2000) Shortage of circulating naive CD8(+) T cells provides new insights on immunodeficiency in aging. Blood 95(9):2860–2868Google Scholar
  18. Finkel T, Serrano M, Blasco MA (2007) The common biology of cancer and ageing. Nature 448(7155):767–774. doi: 10.1038/nature05985 CrossRefGoogle Scholar
  19. Florian MC, Nattamai KJ, Dorr K, Marka G, Uberle B, Vas V, Eckl C, Andra I, Schiemann M, Oostendorp RA, Scharffetter-Kochanek K, Kestler HA, Zheng Y, Geiger H (2013) A canonical to non-canonical Wnt signalling switch in haematopoietic stem-cell ageing. Nature 503(7476):392–396. doi: 10.1038/nature12631 CrossRefGoogle Scholar
  20. Gavazzi G, Krause KH (2002) Ageing and infection. Lancet Infect Dis 2(11):659–666CrossRefGoogle Scholar
  21. Goodwin K, Viboud C, Simonsen L (2006) Antibody response to influenza vaccination in the elderly: a quantitative review. Vaccine 24(8):1159–1169. doi: 10.1016/j.vaccine.2005.08.105 CrossRefGoogle Scholar
  22. Goronzy JJ, Weyand CM (2013) Understanding immunosenescence to improve responses to vaccines. Nat Immunol 14(5):428–436. doi: 10.1038/ni.2588 CrossRefGoogle Scholar
  23. Goronzy JJ, Li G, Yang Z, Weyand CM (2013) The janus head of T cell aging—autoimmunity and immunodeficiency. Front Immunol 4:131. doi: 10.3389/fimmu.2013.00131 CrossRefGoogle Scholar
  24. Grubeck-Loebenstein B, Berger P, Saurwein-Teissl M, Zisterer K, Wick G (1998) No immunity for the elderly. Nat Med 4(8):870CrossRefGoogle Scholar
  25. Haynes L, Swain SL (2012) Aged-related shifts in T cell homeostasis lead to intrinsic T cell defects. Semin Immunol 24(5):350–355. doi: 10.1016/j.smim.2012.04.001 CrossRefGoogle Scholar
  26. Haynes L, Linton PJ, Eaton SM, Tonkonogy SL, Swain SL (1999) Interleukin 2, but not other common gamma chain-binding cytokines, can reverse the defect in generation of CD4 effector T cells from naive T cells of aged mice. J Exp Med 190(7):1013–1024CrossRefGoogle Scholar
  27. Haynes BF, Markert ML, Sempowski GD, Patel DD, Hale LP (2000) The role of the thymus in immune reconstitution in aging, bone marrow transplantation, and HIV-1 infection. Annu Rev Immunol 18:529–560CrossRefGoogle Scholar
  28. Haynes L, Eaton SM, Burns EM, Randall TD, Swain SL (2003) CD4 T cell memory derived from young naive cells functions well into old age, but memory generated from aged naive cells functions poorly. Proc Natl Acad Sci U S A 100(25):15053–15058. doi: 10.1073/pnas.2433717100 CrossRefGoogle Scholar
  29. Hazeldine J, Hampson P, Lord JM (2012) Reduced release and binding of perforin at the immunological synapse underlies the age-related decline in natural killer cell cytotoxicity. Aging Cell 11(5):751–759. doi: 10.1111/j.1474-9726.2012.00839.x CrossRefGoogle Scholar
  30. Herndler-Brandstetter D, Schwaiger S, Veel E, Fehrer C, Cioca DP, Almanzar G, Keller M, Pfister G, Parson W, Wurzner R, Schonitzer D, Henson SM, Aspinall R, Lepperdinger G, Grubeck-Loebenstein B (2005) CD25-expressing CD8+ T cells are potent memory cells in old age. J Immunol 175(3):1566–1574CrossRefGoogle Scholar
  31. Herndler-Brandstetter D, Cioca DP, Grubeck-Loebenstein B (2006) Immunizations in the elderly: do they live up to their promise? Wien Med Wochenschr 156(5–6):130–141. doi: 10.1007/s10354-006-0267-8 CrossRefGoogle Scholar
  32. Herndler-Brandstetter D, Veel E, Laschober GT, Pfister G, Brunner S, Walcher S, Parson W, Lepperdinger G, Grubeck-Loebenstein B (2008) Non-regulatory CD8+CD45RO+CD25+ T-lymphocytes may compensate for the loss of antigen-inexperienced CD8+CD45RA+T-cells in old age. Biol Chem 389(5):561–568CrossRefGoogle Scholar
  33. Herndler-Brandstetter D, Weinberger B, Pfister G, Weiskopf D, Grubeck-Loebenstein B (2011) The aging of the adaptive immune system. Curr Immunol Rev 7:94–103CrossRefGoogle Scholar
  34. Herndler-Brandstetter D, Landgraf K, Tzankov A, Jenewein B, Brunauer R, Laschober GT, Parson W, Kloss F, Gassner R, Lepperdinger G, Grubeck-Loebenstein B (2012) The impact of aging on memory T cell phenotype and function in the human bone marrow. J Leukoc Biol 91(2):197–205. doi: 10.1189/jlb.0611299 CrossRefGoogle Scholar
  35. Holland AM, van den Brink MR (2009) Rejuvenation of the aging T cell compartment. Curr Opin Immunol 21(4):454–459CrossRefGoogle Scholar
  36. Iancu EM, Corthesy P, Baumgaertner P, Devevre E, Voelter V, Romero P, Speiser DE, Rufer N (2009) Clonotype selection and composition of human CD8 T cells specific for persistent herpes viruses varies with differentiation but is stable over time. J Immunol 183(1):319–331CrossRefGoogle Scholar
  37. Johnson SA, Cambier JC (2004) Ageing, autoimmunity and arthritis: senescence of the B cell compartment—implications for humoral immunity. Arthritis Res Ther 6(4):131–139. doi: 10.1186/ar1180 CrossRefGoogle Scholar
  38. Kapasi ZF, Murali-Krishna K, McRae ML, Ahmed R (2002) Defective generation but normal maintenance of memory T cells in old mice. Eur J Immunol 32(6):1567–1573. doi: 10.1002/1521-4141(200206)32:6<1567::AID-IMMU1567>3.0.CO;2-P CrossRefGoogle Scholar
  39. Kovaiou RD, Weiskirchner I, Keller M, Pfister G, Cioca DP, Grubeck-Loebenstein B (2005) Age-related differences in phenotype and function of CD4+ T cells are due to a phenotypic shift from naive to memory effector CD4+ T cells. Int Immunol 17(10):1359–1366. doi: 10.1093/intimm/dxh314 CrossRefGoogle Scholar
  40. Kovaiou RD, Herndler-Brandstetter D, Grubeck-Loebenstein B (2007) Age-related changes in immunity: implications for vaccination in the elderly. Expert Rev Mol Med 9(3):1–17CrossRefGoogle Scholar
  41. Lazuardi L, Jenewein B, Wolf AM, Pfister G, Tzankov A, Grubeck-Loebenstein B (2005) Age-related loss of naive T cells and dysregulation of T-cell/B-cell interactions in human lymph nodes. Immunology 114(1):37–43. doi: 10.1111/j.1365-2567.2004.02006.x CrossRefGoogle Scholar
  42. LeMaoult J, Szabo P, Weksler ME (1997) Effect of age on humoral immunity, selection of the B-cell repertoire and B-cell development. Immunol Rev 160:115–126CrossRefGoogle Scholar
  43. Linton PJ, Dorshkind K (2004) Age-related changes in lymphocyte development and function. Nat Immunol 5(2):133–139. doi: 10.1038/ni1033 CrossRefGoogle Scholar
  44. Lynch HE, Goldberg GL, Chidgey A, Van den Brink MR, Boyd R, Sempowski GD (2009) Thymic involution and immune reconstitution. Trends Immunol 30(7):366–373CrossRefGoogle Scholar
  45. Mattila PS, Tarkkanen J (1997) Age-associated changes in the cellular composition of the human adenoid. Scand J Immunol 45(4):423–427CrossRefGoogle Scholar
  46. McElhaney JE (2009) Prevention of infectious diseases in older adults through immunization: the challenge of the senescent immune response. Expert Rev Vaccines 8(5):593–606CrossRefGoogle Scholar
  47. Messaoudi I, Warner J, Fischer M, Park B, Hill B, Mattison J, Lane MA, Roth GS, Ingram DK, Picker LJ, Douek DC, Mori M, Nikolich-Zugich J (2006) Delay of T cell senescence by caloric restriction in aged long-lived nonhuman primates. Proc Natl Acad Sci U S A 103(51): 19448–19453CrossRefGoogle Scholar
  48. Murali-Krishna K, Ahmed R (2000) Cutting edge: naive T cells masquerading as memory cells. J Immunol 165(4):1733–1737CrossRefGoogle Scholar
  49. Muss HB (2009) Cancer in the elderly: a societal perspective from the United States. Clin Oncol (R Coll Radiol) 21(2):92–98. doi: 10.1016/j.clon.2008.11.008 CrossRefGoogle Scholar
  50. Olsson J, Wikby A, Johansson B, Lofgren S, Nilsson BO, Ferguson FG (2000) Age-related change in peripheral blood T-lymphocyte subpopulations and cytomegalovirus infection in the very old: the Swedish longitudinal OCTO immune study. Mech Ageing Dev 121(1–3):187–201Google Scholar
  51. Oxman MN, Levin MJ, Johnson GR, Schmader KE, Straus SE, Gelb LD, Arbeit RD, Simberkoff MS, Gershon AA, Davis LE, Weinberg A, Boardman KD, Williams HM, Zhang JH, Peduzzi PN, Beisel CE, Morrison VA, Guatelli JC, Brooks PA, Kauffman CA, Pachucki CT, Neuzil KM, Betts RF, Wright PF, Griffin MR, Brunell P, Soto NE, Marques AR, Keay SK, Goodman RP, Cotton DJ, Gnann JW Jr, Loutit J, Holodniy M, Keitel WA, Crawford GE, Yeh SS, Lobo Z, Toney JF, Greenberg RN, Keller PM, Harbecke R, Hayward AR, Irwin MR, Kyriakides TC, Chan CY, Chan IS, Wang WW, Annunziato PW, Silber JL (2005) A vaccine to prevent herpes zoster and postherpetic neuralgia in older adults. N Engl J Med 352(22):2271–2284. doi: 10.1056/NEJMoa051016 CrossRefGoogle Scholar
  52. Palmer DB (2013) The effect of age on thymic function. Front Immunol 4:316. doi: 10.3389/fimmu.2013.00316 CrossRefGoogle Scholar
  53. Pfister G, Weiskopf D, Lazuardi L, Kovaiou RD, Cioca DP, Keller M, Lorbeg B, Parson W, Grubeck-Loebenstein B (2006) Naive T cells in the elderly: are they still there? Ann N Y Acad Sci 1067:152–157. doi: 10.1196/annals.1354.018 CrossRefGoogle Scholar
  54. Rafailidis PI, Mourtzoukou EG, Varbobitis IC, Falagas ME (2008) Severe cytomegalovirus infection in apparently immunocompetent patients: a systematic review. Virol J 5:47. doi: 10.1186/1743-422X-5-47 CrossRefGoogle Scholar
  55. Remmerswaal EB, Havenith SH, Idu MM, van Leeuwen EM, van Donselaar KA, Ten Brinke A, van der Bom-Baylon N, Bemelman FJ, van Lier RA, Ten Berge IJ (2012) Human virus-specific effector-type T cells accumulate in blood but not in lymph nodes. Blood 119(7):1702–1712. doi: 10.1182/blood-2011-09-381574 CrossRefGoogle Scholar
  56. Rongvaux A, Takizawa H, Strowig T, Willinger T, Eynon EE, Flavell RA, Manz MG (2013) Human hemato-lymphoid system mice: current use and future potential for medicine. Annu Rev Immunol 31:635–674. doi: 10.1146/annurev-immunol-032712-095921 CrossRefGoogle Scholar
  57. Rossi DJ, Bryder D, Zahn JM, Ahlenius H, Sonu R, Wagers AJ, Weissman IL (2005) Cell intrinsic alterations underlie hematopoietic stem cell aging. Proc Natl Acad Sci U S A 102(26):9194–9199. doi: 10.1073/pnas.0503280102 CrossRefGoogle Scholar
  58. Rossi DJ, Bryder D, Seita J, Nussenzweig A, Hoeijmakers J, Weissman IL (2007) Deficiencies in DNA damage repair limit the function of haematopoietic stem cells with age. Nature 447(7145):725–729. doi: 10.1038/nature05862 CrossRefGoogle Scholar
  59. Rudd BD, Venturi V, Li G, Samadder P, Ertelt JM, Way SS, Davenport MP, Nikolich-Zugich J (2011) Nonrandom attrition of the naive CD8+ T-cell pool with aging governed by T-cell receptor: pMHC interactions. Proc Natl Acad Sci U S A 108(33):13694–13699. doi: 10.1073/pnas.1107594108 CrossRefGoogle Scholar
  60. Sakaguchi N, Takahashi T, Hata H, Nomura T, Tagami T, Yamazaki S, Sakihama T, Matsutani T, Negishi I, Nakatsuru S, Sakaguchi S (2003) Altered thymic T-cell selection due to a mutation of the ZAP-70 gene causes autoimmune arthritis in mice. Nature 426(6965):454–460. doi: 10.1038/nature02119 CrossRefGoogle Scholar
  61. Sathaliyawala T, Kubota M, Yudanin N, Turner D, Camp P, Thome JJ, Bickham KL, Lerner H, Goldstein M, Sykes M, Kato T, Farber DL (2013) Distribution and compartmentalization of human circulating and tissue-resident memory T cell subsets. Immunity 38(1):187–197. doi: 10.1016/j.immuni.2012.09.020 CrossRefGoogle Scholar
  62. Sauce D, Appay V (2011) Altered thymic activity in early life: how does it affect the immune system in young adults? Curr Opin Immunol 23(4):543–548. doi: 10.1016/j.coi.2011.05.001 CrossRefGoogle Scholar
  63. Saurwein-Teissl M, Lung TL, Marx F, Gschosser C, Asch E, Blasko I, Parson W, Bock G, Schonitzer D, Trannoy E, Grubeck-Loebenstein B (2002) Lack of antibody production following immunization in old age: association with CD8(+)CD28(-) T cell clonal expansions and an imbalance in the production of Th1 and Th2 cytokines. J Immunol 168(11):5893–5899CrossRefGoogle Scholar
  64. Schwaiger S, Wolf AM, Robatscher P, Jenewein B, Grubeck-Loebenstein B (2003) IL-4-producing CD8+ T cells with a CD62L++(bright) phenotype accumulate in a subgroup of older adults and are associated with the maintenance of intact humoral immunity in old age. J Immunol 170(1):613–619CrossRefGoogle Scholar
  65. Shahaf GL, Hazanov H, Averbuch D, Amu S, Ademokun A, Wu Y-C, Dunn-Walters D, Chiodi F, Mehr R (2014) Understanding the mechanisms of immune system aging: immune system cell development and antibody repertoires. In: Leist AK, Kulmala J, Nyqvist F (eds) Health and cognition in old age. Springer, New YorkGoogle Scholar
  66. Shaw AC, Goldstein DR, Montgomery RR (2013) Age-dependent dysregulation of innate immunity. Nat Rev Immunol 13(12):875–887. doi: 10.1038/nri3547 CrossRefGoogle Scholar
  67. Steinmann GG, Klaus B, Muller-Hermelink HK (1985) The involution of the ageing human thymic epithelium is independent of puberty. A morphometric study. Scand J Immunol 22(5): 563–575CrossRefGoogle Scholar
  68. Surani MA, McLaren A (2006) Stem cells: a new route to rejuvenation. Nature 443(7109): 284–285CrossRefGoogle Scholar
  69. Valenzuela HF, Effros RB (2002) Divergent telomerase and CD28 expression patterns in human CD4 and CD8 T cells following repeated encounters with the same antigenic stimulus. Clin Immunol 105(2):117–125CrossRefGoogle Scholar
  70. Weinberger B, Lazuardi L, Weiskirchner I, Keller M, Neuner C, Fischer KH, Neuman B, Wurzner R, Grubeck-Loebenstein B (2007) Healthy aging and latent infection with CMV lead to distinct changes in CD8+ and CD4+ T-cell subsets in the elderly. Hum Immunol 68(2):86–90. doi: 10.1016/j.humimm.2006.10.019 CrossRefGoogle Scholar
  71. Weinberger B, Herndler-Brandstetter D, Schwanninger A, Weiskopf D, Grubeck-Loebenstein B (2008) Biology of immune responses to vaccines in elderly persons. Clin Infect Dis 46(7):1078–1084. doi: 10.1086/529197 CrossRefGoogle Scholar
  72. Weinberger B, Welzl K, Herndler-Brandstetter D, Parson W, Grubeck-Loebenstein B (2009) CD28(-)CD8(+) T cells do not contain unique clonotypes and are therefore dispensable. Immunol Lett 127(1):27–32CrossRefGoogle Scholar
  73. Weksler ME, Szabo P (2000) The effect of age on the B-cell repertoire. J Clin Immunol 20(4): 240–249CrossRefGoogle Scholar
  74. Weyand CM, Fujii H, Shao L, Goronzy JJ (2009) Rejuvenating the immune system in rheumatoid arthritis. Nat Rev Rheumatol 5(10):583–588. doi: 10.1038/nrrheum.2009.180 CrossRefGoogle Scholar
  75. Yager EJ, Ahmed M, Lanzer K, Randall TD, Woodland DL, Blackman MA (2008) Age-associated decline in T cell repertoire diversity leads to holes in the repertoire and impaired immunity to influenza virus. J Exp Med 205(3):711–723. doi: 10.1084/jem.20071140 CrossRefGoogle Scholar
  76. Yang H, Youm YH, Dixit VD (2009a) Inhibition of thymic adipogenesis by caloric restriction is coupled with reduction in age-related thymic involution. J Immunol 183(5):3040–3052CrossRefGoogle Scholar
  77. Yang H, Youm YH, Vandanmagsar B, Rood J, Kumar KG, Butler AA, Dixit VD (2009b) Obesity accelerates thymic aging. Blood 114(18):3803–3812CrossRefGoogle Scholar
  78. Zanni F, Vescovini R, Biasini C, Fagnoni F, Zanlari L, Telera A, Di Pede P, Passeri G, Pedrazzoni M, Passeri M, Franceschi C, Sansoni P (2003) Marked increase with age of type 1 cytokines within memory and effector/cytotoxic CD8+ T cells in humans: a contribution to understand the relationship between inflammation and immunosenescence. Exp Gerontol 38(9):981–987CrossRefGoogle Scholar

Copyright information

© Springer International Publishing Switzerland 2014

Authors and Affiliations

  1. 1.Department of ImmunobiologyYale University School of MedicineNew HavenUSA

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