Skip to main content
SpringerLink
Log in

Innate Immunosenescence and Its Impact on Health in Old Age

  • Chapter
  • First Online:
The Ageing Immune System and Health

  • 1294 Accesses

Abstract

Physiological ageing is associated with significant re-modelling of the immune system. Termed immunosenescence, age-related changes have been described in the composition, phenotype and function of both the innate and adaptive arms of the immune system. As the first line of defence against invading pathogens, age-associated alterations in innate immunity have been linked to the increased infection-related morbidity and mortality rates reported by older adults. However, is the only consequence of innate immunosenescence an increased susceptibility to infection? With data emerging demonstrating a role for innate immune cells in other biological processes besides host protection, such as wound healing, clearance of senescent cells and the resolution of inflammation, it is likely that innate immunosenescence has more far reaching consequences for the health and well-being of older adults than originally thought. Here, we provide an overview of the alterations that occur in innate immunity with age, highlighting studies that have uncovered the molecular mechanisms that underlie the changes they describe. Furthermore, we discuss the possible implications of innate immunosenescence for older adults beyond the much-discussed increased incidence and severity of infection.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution
eBook
USD 16.99
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 54.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 54.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

References

  1. United Nations Department of Economic and Social Affairs Population Division. World Population Ageing 1950–2050. Executive Summary. http://www.un.org/esa/population/publications/worldageing19502050/ (2016). Accessed on 03 Jan 2016

  2. Comfort A. Ageing: the biology of senescence. London: Routledge and Kegan Paul; 1964. p. 365.

    Google Scholar 

  3. Emori TG, Banerjee SN, Culver DH, Gaynes RP, Horan TC, Edwards JR, et al. Nosocomial infections in elderly patients in the United States, 1986–1990. National Nosocomial Infections Surveillance System. Am J Med. 1991;91:289S–93.

    Article  CAS  PubMed  Google Scholar 

  4. Fleming DM, Elliot AJ. The impact of influenza on the health and health care utilisation of elderly people. Vaccine. 2005;23 Suppl 1:S1–9.

    Article  PubMed  Google Scholar 

  5. Marston BJ, Plouffe JF, File Jr TM, Hackman BA, Salstrom SJ, Lipman HB, et al. Incidence of community-acquired pneumonia requiring hospitalization. Results of a population-based active surveillance Study in Ohio. The Community-Based Pneumonia Incidence Study Group. Arch Intern Med. 1997;157:1709–18.

    Article  CAS  PubMed  Google Scholar 

  6. Thompson WW, Shay DK, Weintraub E, Brammer L, Cox N, Anderson LJ, et al. Mortality associated with influenza and respiratory syncytial virus in the United States. JAMA. 2003;289:179–86.

    Article  PubMed  Google Scholar 

  7. Fein AM. Pneumonia in the elderly: overview of diagnostic and therapeutic approaches. Clin Infect Dis. 1999;28:726–9.

    Article  CAS  PubMed  Google Scholar 

  8. Aw D, Silva AB, Palmer DB. Immunosenescence: emerging challenges for an ageing population. Immunology. 2007;120:435–46.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  9. Ho JC, Chan KN, Hu WH, Lam WK, Zheng L, Tiope GL, et al. The effect of aging on nasal mucociliary clearance, beat frequency, and ultrastructure of respiratory cilia. Am J Respir Crit Care Med. 2001;163:983–8.

    Article  CAS  PubMed  Google Scholar 

  10. Nagaki K, Hiramatsu S, Inai S, Sasaki A. The effect of aging on complement activity (CH50) and complement protein levels. J Clin Lab Immunol. 1980;3:45–50.

    Article  CAS  PubMed  Google Scholar 

  11. Sagiv A, Biran A, Yon M, Simon J, Lowe SW, Krizhanovsky V. Granule exocytosis mediates immune surveillance of senescent cells. Oncogene. 2013;32:1971–7.

    Article  CAS  PubMed  Google Scholar 

  12. Thoren FB, Riise RE, Ousback J, Della Chiesa M, Alsterholm M, Marcenaro E, et al. Human NK Cells induce neutrophil apoptosis via an NKp46- and Fas-dependent mechanism. J Immunol. 2012;188:1668–74.

    Article  CAS  PubMed  Google Scholar 

  13. Waggoner SN, Cornberg M, Selin LK, Welsh RM. Natural killer cells act as rheostats modulating antiviral T cells. Nature. 2012;481:394–8.

    CAS  Google Scholar 

  14. Guo S, DiPietro LA. Factors affecting wound healing. J Dent Res. 2010;89:219–29.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  15. Sapey E, Greenwood H, Walton G, Mann E, Love A, Aaronson N, et al. Phosphoinositide 3-kinase inhibition restores neutrophil accuracy in the elderly: toward targeted treatments for immunosenescence. Blood. 2014;123:239–48.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  16. Niwa Y, Kasama T, Miyachi Y, Kanoh T. Neutrophil chemotaxis, phagocytosis and parameters of reactive oxygen species in human aging: cross-sectional and longitudinal studies. Life Sci. 1989;44:1655–64.

    Article  CAS  PubMed  Google Scholar 

  17. Fulop T, Larbi A, Douziech N, Fortin C, Guerard KP, Lesur O, et al. Signal transduction and functional changes in neutrophils with aging. Aging Cell. 2004;3:217–26.

    Article  CAS  PubMed  Google Scholar 

  18. Biasi D, Bambara LM, Carletto A, Caramaschi P, Andrioli G, Urbani G, et al. Neutrophil migration, oxidative metabolism and adhesion in early onset periodontitis. J Clin Periodontol. 1999;26:563–8.

    Article  CAS  PubMed  Google Scholar 

  19. Brubaker AL, Rendon JL, Ramirez L, Choudhry MA, Kovacs EJ. Reduced neutrophil chemotaxis and infiltration contributes to delayed resolution of cutaneous wound infection with advanced age. J Immunol. 2013;190:1746–57.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  20. Nacionales DC, Szpila B, Ungaro R, Lopez MC, Zhang J, Gentile LF, et al. A detailed characterization of the dysfunctional immunity and abnormal myelopoiesis induced by severe shock and trauma in the aged. J Immunol. 2015;195:2396–407.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  21. Emanuelli G, Lanzio M, Anfossi T, Romano S, Anfossi G, Calcamuggi G. Influence of age on polymorphonuclear leukocytes in vitro: phagocytic activity in healthy human subjects. Gerontology. 1986;32:308–16.

    Article  CAS  PubMed  Google Scholar 

  22. Butcher SK, Chahal H, Nayak L, Sinclair A, Henriquez NV, Sapey E, et al. Senescence in innate immune responses: reduced neutrophil phagocytic capacity and CD16 expression in elderly humans. J Leukoc Biol. 2001;70:881–6.

    CAS  PubMed  Google Scholar 

  23. Wenisch C, Patruta S, Daxbock F, Krause R, Horl W. Effect of age on human neutrophil function. J Leukoc Biol. 2000;67:40–5.

    CAS  PubMed  Google Scholar 

  24. Simell B, Vuorela A, Ekstrom N, Palmu A, Reunanen A, Meri S, et al. Aging reduces the functionality of anti-pneumococcal antibodies and the killing of Streptococcus pneumoniae by neutrophil phagocytosis. Vaccine. 2011;29:1929–34.

    Article  CAS  PubMed  Google Scholar 

  25. Braga PC, Sala MT, Dal SM, Pecile A, Annoni G, Vergani C. Age-associated differences in neutrophil oxidative burst (chemiluminescence). Exp Gerontol. 1998;33:477–84.

    Article  CAS  PubMed  Google Scholar 

  26. Brinkmann V, Reichard U, Goosmann C, Fauler B, Uhlemann Y, Weiss DS, et al. Neutrophil extracellular traps kill bacteria. Science. 2004;303:1532–5.

    Article  CAS  PubMed  Google Scholar 

  27. Tseng CW, Kyme PA, Arruda A, Ramanujan VK, Tawackoli W, Liu GY. Innate immune dysfunctions in aged mice facilitate the systemic dissemination of methicillin-resistant S. aureus. PLoS One. 2012;7:e41454.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  28. Hazeldine J, Harris P, Chapple IL, Grant M, Greenwood H, Livesey A, et al. Impaired neutrophil extracellular trap formation: a novel defect in the innate immune system of aged individuals. Aging Cell. 2014;13:690–8.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  29. Bianchi M, Hakkim A, Brinkmann V, Siler U, Seger RA, Zychlinsky A, et al. Restoration of NET formation by gene therapy in CGD controls aspergillosis. Blood. 2009;114:2619–22.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  30. Alvarez E, Ruiz-Gutierrez V, Sobrino F, Santa-Maria C. Age-related changes in membrane lipid composition, fluidity and respiratory burst in rat peritoneal neutrophils. Clin Exp Immunol. 2001;124:95–102.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  31. Fortin CF, Lesur O, Fulop Jr T. Effects of aging on triggering receptor expressed on myeloid cells (TREM)-1-induced PMN functions. FEBS Lett. 2007;581:1173–8.

    Article  CAS  PubMed  Google Scholar 

  32. Zhang Y, Wallace DL, de Lara CM, Ghattas H, Asquith B, Worth A, et al. In vivo kinetics of human natural killer cells: the effects of ageing and acute and chronic viral infection. Immunology. 2007;121:258–65.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  33. Hazeldine J, Hampson P, Lord JM. Reduced release and binding of perforin at the immunological synapse underlies the age-related decline in natural killer cell cytotoxicity. Aging Cell. 2012;11:751–9.

    Article  CAS  PubMed  Google Scholar 

  34. Lutz CT, Karapetyan A, Al-Attar A, Shelton BJ, Holt KJ, Tucker JH, et al. Human NK cells proliferate and die in vivo more rapidly than T cells in healthy young and elderly adults. J Immunol. 2011;186:4590–8.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  35. Hayhoe RP, Henson SM, Akbar AN, Palmer DB. Variation of human natural killer cell phenotypes with age: identification of a unique KLRG1-negative subset. Hum Immunol. 2010;71:676–81.

    Article  CAS  PubMed  Google Scholar 

  36. Beli E, Clinthorne JF, Duriancik DM, Hwang I, Kim S, Gardner EM. Natural killer cell function is altered during the primary response of aged mice to influenza infection. Mech Ageing Dev. 2011;132:503–10.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  37. Fang M, Roscoe F, Sigal LJ. Age-dependent susceptibility to a viral disease due to decreased natural killer cell numbers and trafficking. J Exp Med. 2010;207:2369–81.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  38. Mariani E, Meneghetti A, Neri S, Ravaglia G, Forti P, Cattini L, et al. Chemokine production by natural killer cells from nonagenarians. Eur J Immunol. 2002;32:1524–9.

    Article  CAS  PubMed  Google Scholar 

  39. Smyth MJ, Cretney E, Kelly JM, Westwood JA, Street SE, Yagita H, et al. Activation of NK cell cytotoxicity. Mol Immunol. 2005;42:501–10.

    Article  CAS  PubMed  Google Scholar 

  40. Hazeldine J, Lord JM. The impact of ageing on natural killer cell function and potential consequences for health in older adults. Ageing Res Rev. 2013;12:1069–78.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  41. Almeida-Oliveira A, Smith-Carvalho M, Porto LC, Cardoso-Oliveira J, Ribeiro Ados S, Falcao RR, et al. Age-related changes in natural killer cell receptors from childhood through old age. Hum Immunol. 2011;72:319–29.

    Article  CAS  PubMed  Google Scholar 

  42. Facchini A, Mariani E, Mariani AR, Papa S, Vitale M, Manzoli FA. Increased number of circulating Leu 11+ (CD 16) large granular lymphocytes and decreased NK activity during human ageing. Clin Exp Immunol. 1987;68:340–7.

    CAS  PubMed  PubMed Central  Google Scholar 

  43. Mariani E, Mariani AR, Meneghetti A, Tarozzi A, Cocco L, Facchini A. Age-dependent decreases of NK cell phosphoinositide turnover during spontaneous but not Fc-mediated cytolytic activity. Int Immunol. 1998;10:981–9.

    Article  CAS  PubMed  Google Scholar 

  44. Vitale M, Della CM, Carlomagno S, Pende D, Arico M, Moretta L, et al. NK-dependent DC maturation is mediated by TNFalpha and IFNgamma released upon engagement of the NKp30 triggering receptor. Blood. 2005;106:566–71.

    Article  CAS  PubMed  Google Scholar 

  45. Krishnaraj R, Bhooma T. Cytokine sensitivity of human NK cells during immunosenescence. 2. IL2-induced interferon gamma secretion. Immunol Let. 1996;50:59.

    Article  CAS  Google Scholar 

  46. Mariani E, Pulsatelli L, Meneghetti A, Dolzani P, Mazzetti I, Neri S, et al. Different IL-8 production by T and NK lymphocytes in elderly subjects. Mech Ageing Dev. 2001;122:1383–95.

    Article  CAS  PubMed  Google Scholar 

  47. Chiu BC, Stolberg VR, Chensue SW. Mononuclear phagocyte-derived IL-10 suppresses the innate IL-12/IFN-gamma axis in lung-challenged aged mice. J Immunol. 2008;181:3156–66.

    Article  CAS  PubMed  Google Scholar 

  48. Biron CA, Byron KS, Sullivan JL. Severe herpesvirus infections in an adolescent without natural killer cells. N Engl J Med. 1989;320:1731–5.

    Article  CAS  PubMed  Google Scholar 

  49. Ogata K, Yokose N, Tamura H, An E, Nakamura K, Dan K, et al. Natural killer cells in the late decades of human life. Clin Immunol Immunopathol. 1997;84:269–75.

    Article  CAS  PubMed  Google Scholar 

  50. Ogata K, An E, Shioi Y, Nakamura K, Luo S, Yokose N, et al. Association between natural killer cell activity and infection in immunologically normal elderly people. Clin Exp Immunol. 2001;124:392–7.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  51. Levy SM, Herberman RB, Lee J, Whiteside T, Beadle M, Heiden L, et al. Persistently low natural killer cell activity, age, and environmental stress as predictors of infectious morbidity. Nat Immun Cell Growth Regul. 1991;10:289–307.

    CAS  PubMed  Google Scholar 

  52. Mysliwska J, Trzonkowski P, Szmit E, Brydak LB, Machala M, Mysliwski A. Immunomodulating effect of influenza vaccination in the elderly differing in health status. Exp Gerontol. 2004;39:1447–58.

    Article  CAS  PubMed  Google Scholar 

  53. Wong KL, Yeap WH, Tai JJ, Ong SM, Dang TM, Wong SC. The three human monocyte subsets: implications for health and disease. Immunol Res. 2012;53:41–57.

    Article  CAS  PubMed  Google Scholar 

  54. Qian F, Wang X, Zhang L, Chen S, Piecychna M, Allore H, et al. Age-associated elevation in TLR5 leads to increased inflammatory responses in the elderly. Aging Cell. 2012;11:104–10.

    Article  CAS  PubMed  Google Scholar 

  55. Seidler S, Zimmermann HW, Bartneck M, Trautwein C, Tacke F. Age-dependent alterations of monocyte subsets and monocyte-related chemokine pathways in healthy adults. BMC Immunol. 2010;11:30.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  56. Hearps AC, Martin GE, Angelovich TA, Cheng WJ, Maisa A, Landay AL, et al. Aging is associated with chronic innate immune activation and dysregulation of monocyte phenotype and function. Aging Cell. 2012;11:867–75.

    Article  CAS  PubMed  Google Scholar 

  57. Nyugen J, Agrawal S, Gollapudi S, Gupta S. Impaired functions of peripheral blood monocyte subpopulations in aged humans. J Clin Immunol. 2010;30:806–13.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  58. Takeda K, Kaisho T, Akira S. Toll-like receptors. Annu Rev Immunol. 2003;21:335–76.

    Article  CAS  PubMed  Google Scholar 

  59. van Duin D, Mohanty S, Thomas V, Ginter S, Montgomery RR, Fikrig E, et al. Age-associated defect in human TLR-1/2 function. J Immunol. 2007;178:970–5.

    Article  CAS  PubMed  Google Scholar 

  60. Lim JS, Nguyen KC, Nguyen CT, Jang IS, Han JM, Fabian C, et al. Flagellin-dependent TLR5/caveolin-1 as a promising immune activator in immunosenescence. Aging Cell. 2015;14:907–15.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  61. Taylor DN, Treanor JJ, Strout C, Johnson C, Fitzgerald T, Kavita U, et al. Induction of a potent immune response in the elderly using the TLR-5 agonist, flagellin, with a recombinant hemagglutinin influenza-flagellin fusion vaccine (VAX125, STF2.HA1 SI). Vaccine. 2011;29:4897–902.

    Article  CAS  PubMed  Google Scholar 

  62. van Duin D, Allore HG, Mohanty S, Ginter S, Newman FK, Belshe RB, et al. Prevaccine determination of the expression of costimulatory B7 molecules in activated monocytes predicts influenza vaccine responses in young and older adults. J Infect Dis. 2007;195:1590–7.

    Article  CAS  PubMed  Google Scholar 

  63. Olivieri F, Procopio AD, Montgomery RR. Effect of aging on microRNAs and regulation of pathogen recognition receptors. Curr Opin Immunol. 2014;29:29–37.

    Article  CAS  PubMed  Google Scholar 

  64. Renshaw M, Rockwell J, Engleman C, Gewirtz A, Katz J, Sambhara S. Cutting edge: impaired Toll-like receptor expression and function in aging. J Immunol. 2002;169:4697–701.

    Article  CAS  PubMed  Google Scholar 

  65. Boehmer ED, Goral J, Faunce DE, Kovacs EJ. Age-dependent decrease in Toll-like receptor 4-mediated proinflammatory cytokine production and mitogen-activated protein kinase expression. J Leukoc Biol. 2004;75:342–9.

    Article  CAS  PubMed  Google Scholar 

  66. Boehmer ED, Meehan MJ, Cutro BT, Kovacs EJ. Aging negatively skews macrophage. Mech Ageing Dev. 2005;126:1305–13.

    Article  CAS  PubMed  Google Scholar 

  67. Chelvarajan RL, Collins SM, Van Willigen JM, Bondada S. The unresponsiveness of aged mice to polysaccharide antigens is a result of a defect in macrophage function. J Leukoc Biol. 2005;77:503–12.

    Article  CAS  PubMed  Google Scholar 

  68. Corsini E, Battaini F, Lucchi L, Marinovich M, Racchi M, Govoni S, et al. A defective protein kinase C anchoring system underlying age-associated impairment in TNF-alpha production in rat macrophages. J Immunol. 1999;163:3468–73.

    CAS  PubMed  Google Scholar 

  69. Jiang M, Xiang Y, Wang D, Gao J, Liu D, Liu Y, et al. Dysregulated expression of miR-146a contributes to age-related dysfunction of macrophages. Aging Cell. 2012;11:29–40.

    Article  CAS  PubMed  Google Scholar 

  70. Agius E, Lacy KE, Vukmanovic-Stejic M, Jagger AL, Papageorgiou AP, Hall S, et al. Decreased TNF-alpha synthesis by macrophages restricts cutaneous immunosurveillance by memory CD4+ T cells during aging. J Exp Med. 2009;206:1929–40.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  71. Agrawal A, Agrawal S, Cao JN, Su H, Osann K, Gupta S. Altered innate immune functioning of dendritic cells in elderly humans: a role of phosphoinositide 3-kinase-signaling pathway. J Immunol. 2007;178:6912–22.

    Article  CAS  PubMed  Google Scholar 

  72. Jing Y, Shaheen E, Drake RR, Chen N, Gravenstein S, Deng Y. Aging is associated with a numerical and functional decline in plasmacytoid dendritic cells, whereas myeloid dendritic cells are relatively unaltered in human peripheral blood. Hum Immunol. 2009;70:777–84.

    Article  CAS  PubMed  Google Scholar 

  73. Panda A, Qian F, Mohanty S, Van Duin D, Newman FK, Zhang L, et al. Age-associated decrease in TLR function in primary human dendritic cells predicts influenza vaccine response. J Immunol. 2010;184:2518–27.

    Article  CAS  PubMed  Google Scholar 

  74. Canaday DH, Amponsah NA, Jones L, Tisch DJ, Hornick TR, Ramachandra L. Influenza-induced production of interferon-alpha is defective in geriatric individuals. J Clin Immunol. 2010;30:373–83.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  75. Della BS, Bierti L, Presicce P, Arienti R, Valenti M, Saresella M, et al. Peripheral blood dendritic cells and monocytes are differently regulated in the elderly. Clin Immunol. 2007;122:220–8.

    Article  CAS  Google Scholar 

  76. Bhushan M, Cumberbatch M, Dearman RJ, Andrew SM, Kimber I, Griffiths CE. Tumour necrosis factor-alpha-induced migration of human Langerhans cells: the influence of ageing. Br J Dermatol. 2002;146:32–40.

    Article  CAS  PubMed  Google Scholar 

  77. Shodell M, Siegal FP. Circulating, interferon-producing plasmacytoid dendritic cells decline during human ageing. Scand J Immunol. 2002;56:518–21.

    Article  CAS  PubMed  Google Scholar 

  78. Agrawal A, Gupta S. Impact of aging on dendritic cell functions in humans. Ageing Res Rev. 2011;10:336–45.

    Article  CAS  PubMed  Google Scholar 

  79. Sridharan A, Esposo M, Kaushal K, Tay J, Osann K, Agrawal S, et al. Age-associated impaired plasmacytoid dendritic cell functions lead to decreased CD4 and CD8 T cell immunity. Age (Dordr). 2011;33:363–76.

    Article  CAS  Google Scholar 

  80. Stout-Delgado HW, Yang X, Walker WE, Tesar BM, Goldstein DR. Aging impairs IFN regulatory factor 7 up-regulation in plasmacytoid dendritic cells during TLR9 activation. J Immunol. 2008;181:6747–56.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  81. Grolleau-Julius A, Harning EK, Abernathy LM, Yung RL. Impaired dendritic cell function in aging leads to defective antitumor immunity. Cancer Res. 2008;68:6341–9.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  82. Zhao J, Zhao J, Legge K, Perlman S. Age-related increases in PGD(2) expression impair respiratory DC migration, resulting in diminished T cell responses upon respiratory virus infection in mice. J Clin Invest. 2011;121:4921–30.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  83. Liu WM, Nahar TE, Jacobi RH, Gijzen K, Van Beek J, Hak E, et al. Impaired production of TNF-alpha by dendritic cells of older adults leads to a lower CD8+ T cell response against influenza. Vaccine. 2012;30:1659–66.

    Article  CAS  PubMed  Google Scholar 

  84. Donnini A, Argentati K, Mancini R, Smorlesi A, Bartozzi B, Bernardini G, et al. Phenotype, antigen-presenting capacity, and migration of antigen-presenting cells in young and old age. Exp Gerontol. 2002;37:1097–112.

    Article  CAS  PubMed  Google Scholar 

  85. Tesar BM, Walker WE, Unternaehrer J, Joshi NS, Chandele A, Haynes L, et al. Murine [corrected] myeloid dendritic cell-dependent toll-like receptor immunity is preserved with aging. Aging Cell. 2006;5:473–86.

    Article  CAS  PubMed  Google Scholar 

  86. Grolleau-Julius A, Garg MR, Mo R, Stoolman LL, Yung RL. Effect of aging on bone marrow-derived murine CD11c + CD4-CD8alpha- dendritic cell function. J Gerontol A Biol Sci Med Sci. 2006;61:1039–47.

    Article  PubMed  Google Scholar 

  87. Wong CP, Magnusson KR, Ho E. Aging is associated with altered dendritic cells subset distribution and impaired proinflammatory cytokine production. Exp Gerontol. 2010;45:163–9.

    Article  CAS  PubMed  Google Scholar 

  88. Ferlazzo G, Tsang ML, Moretta L, Melioli G, Steinman RM, Munz C. Human dendritic cells activate resting natural killer (NK) cells and are recognized via the NKp30 receptor by activated NK cells. J Exp Med. 2002;195:343–51.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  89. Brancato SK, Albina JE. Wound macrophages as key regulators of repair: origin, phenotype, and function. Am J Pathol. 2011;178:19–25.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  90. Dimri GP, Lee X, Basile G, Acosta M, Scott G, Roskelley C, et al. A biomarker that identifies senescent human cells in culture and in aging skin in vivo. Proc Natl Acad Sci U S A. 1995;92:9363–7.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  91. Price JS, Waters JG, Darrah C, Pennington C, Edwards DR, Donell ST, et al. The role of chondrocyte senescence in osteoarthritis. Aging Cell. 2002;1:57–65.

    Article  CAS  PubMed  Google Scholar 

  92. Baker DJ, Wijshake T, Tchkonia T, LeBrasseur NK, Childs BG, van de Sluis B, et al. Clearance of p16Ink4a-positive senescent cells delays ageing-associated disorders. Nature. 2011;479:232–6.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  93. Krizhanovsky V, Yon M, Dickins RA, Hearn S, Simon J, Miething C, et al. Senescence of activated stellate cells limits liver fibrosis. Cell. 2008;134:657–67.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  94. Xue W, Zender L, Miething C, Dickins RA, Hernando E, Krizhanovsky V, et al. Senescence and tumour clearance is triggered by p53 restoration in murine liver carcinomas. Nature. 2007;445:656–60.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  95. Zhu Y, Tchkonia T, Pirtskhalava T, Gower AC, Ding H, Giorgadze N, et al. The Achilles’ heel of senescent cells: from transcriptome to senolytic drugs. Aging Cell. 2015;14:644–58.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  96. Swift ME, Burns AL, Gray KL, DiPietro LA. Age-related alterations in the inflammatory response to dermal injury. J Invest Dermatol. 2001;117:1027–35.

    Article  CAS  PubMed  Google Scholar 

  97. Hager K, Machein U, Krieger S, Platt D, Seefried G, Bauer J. Interleukin-6 and selected plasma proteins in healthy persons of different ages. Neurobiol Aging. 1994;15:771–2.

    Article  CAS  PubMed  Google Scholar 

  98. Pedersen M, Bruunsgaard H, Weis N, Hendel HW, Andreassen BU, Eldrup E, et al. Circulating levels of TNF-alpha and IL-6-relation to truncal fat mass and muscle mass in healthy elderly individuals and in patients with type-2 diabetes. Mech Ageing Dev. 2003;124:495–502.

    Article  CAS  PubMed  Google Scholar 

  99. Lio D, Scola L, Crivello A, Colonna-Romano G, Candore G, Bonafe M, et al. Gender-specific association between -1082 IL-10 promoter polymorphism and longevity. Genes Immun. 2002;3:30–3.

    Article  CAS  PubMed  Google Scholar 

  100. Bruunsgaard H, Andersen-Ranberg K, Jeune B, Pedersen AN, Skinhoj P, Pedersen BK. A high plasma concentration of TNF-alpha is associated with dementia in centenarians. J Gerontol A Biol Sci Med Sci. 1999;54:M357–64.

    Article  CAS  PubMed  Google Scholar 

  101. Minamino T, Miyauchi H, Yoshida T, Ishida Y, Yoshida H, Komuro I. Endothelial cell senescence in human atherosclerosis: role of telomere in endothelial dysfunction. Circulation. 2002;105:1541–4.

    Article  CAS  PubMed  Google Scholar 

  102. Roggia C, Gao Y, Cenci S, Weitzmann MN, Toraldo G, Isaia G, et al. Up-regulation of TNF-producing T cells in the bone marrow: a key mechanism by which estrogen deficiency induces bone loss in vivo. Proc Natl Acad Sci U S A. 2001;98:13960–5.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  103. Bruunsgaard H, Ladelund S, Pedersen AN, Schroll M, Jorgensen T, Pedersen BK. Predicting death from tumour necrosis factor-alpha and interleukin-6 in 80-year-old people. Clin Exp Immunol. 2003;132:24–31.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  104. Harris TB, Ferrucci L, Tracy RP, Corti MC, Wacholder S, Ettinger Jr WH, et al. Associations of elevated interleukin-6 and C-reactive protein levels with mortality in the elderly. Am J Med. 1999;106:506–12.

    Article  CAS  PubMed  Google Scholar 

  105. Gussekloo J, Schaap MC, Frolich M, Blauw GJ, Westendorp RG. C-reactive protein is a strong but nonspecific risk factor of fatal stroke in elderly persons. Arterioscler Thromb Vasc Biol. 2000;20:1047–51.

    Article  CAS  PubMed  Google Scholar 

  106. Baylis D, Bartlett DB, Syddall HE, Ntani G, Gale CR, Cooper C, et al. Immune-endocrine biomarkers as predictors of frailty and mortality: a 10-year longitudinal study in community-dwelling older people. Age (Dordr). 2013;35:963–71.

    Article  CAS  Google Scholar 

  107. Bruunsgaard H, Skinhoj P, Pedersen AN, Schroll M, Pedersen BK. Ageing, tumour necrosis factor-alpha (TNF-alpha) and atherosclerosis. Clin Exp Immunol. 2000;121:255–60.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  108. Visser M, Pahor M, Taaffe DR, Goodpaster BH, Simonsick EM, Newman AB, et al. Relationship of interleukin-6 and tumor necrosis factor-alpha with muscle mass and muscle strength in elderly men and women: the Health ABC Study. J Gerontol A Biol Sci Med Sci. 2002;57:M326–32.

    Article  PubMed  Google Scholar 

  109. Chow OA, von Kockritz-Blickwede M, Bright AT, Hensler ME, Zinkernagel AS, Cogen AL, et al. Statins enhance formation of phagocyte extracellular traps. Cell Host Microbe. 2010;8:445–54.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  110. Verschoor CP, Johnstone J, Millar J, Dorrington MG, Habibagahi M, Lelic A, et al. Blood CD33(+)HLA-DR(-) myeloid-derived suppressor cells are increased with age and a history of cancer. J Leukoc Biol. 2013;93:633–7.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  111. Bueno V, Sant’Anna OA, Lord JM. Ageing and myeloid-derived suppressor cells: possible involvement in immunosenescence and age-related disease. Age (Dordr). 2014;36:9729.

    Article  CAS  Google Scholar 

  112. Wesolowski R, Markowitz J, Carson III WE. Myeloid derived suppressor cells - a new therapeutic target in the treatment of cancer. J Immunother Cancer. 2013;1:10.

    Article  PubMed  PubMed Central  Google Scholar 

  113. McLachlan JA, Serkin CD, Morrey KM, Bakouche O. Antitumoral properties of aged human monocytes. J Immunol. 1995;154:832–43.

    CAS  PubMed  Google Scholar 

  114. Ashcroft GS, Horan MA, Ferguson MW. Aging alters the inflammatory and endothelial cell adhesion molecule profiles during human cutaneous wound healing. Lab Invest. 1998;78:47–58.

    CAS  PubMed  Google Scholar 

  115. Herrero C, Sebastian C, Marques L, Comalada M, Xaus J, Valledor AF, et al. Immunosenescence of macrophages: reduced MHC class II gene expression. Exp Gerontol. 2002;37:389–94.

    Article  CAS  PubMed  Google Scholar 

  116. Hilmer SN, Cogger VC, Le Couteur DG. Basal activity of Kupffer cells increases with old age. J Gerontol A Biol Sci Med Sci. 2007;62:973–8.

    Article  PubMed  Google Scholar 

  117. Videla LA, Tapia G, Fernandez V. Influence of aging on Kupffer cell respiratory activity in relation to particle phagocytosis and oxidative stress parameters in mouse liver. Redox Rep. 2001;6:155–9.

    Article  CAS  PubMed  Google Scholar 

  118. Ortega E, Garcia JJ, de la Fuente M. Modulation of adherence and chemotaxis of macrophages by norepinephrine. Influence of ageing. Mol Cell Biochem. 2000;203:113–7.

    Article  CAS  PubMed  Google Scholar 

  119. Smallwood HS, Lopez-Ferrer D, Squier TC. Aging enhances the production of reactive oxygen species and bactericidal activity in peritoneal macrophages by upregulating classical activation pathways. Biochemistry. 2011;50:9911–22.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. MRC-ARUK Centre for Musculoskeletal Ageing Research, Institute of Inflammation and Ageing, Birmingham University Medical School, Birmingham, B15 2TT, UK

    Mohammad Ahsan Tariq, Jon Hazeldine & Janet M. Lord

Authors
  1. Mohammad Ahsan Tariq
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Jon Hazeldine
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Janet M. Lord
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Janet M. Lord .

Editor information

Editors and Affiliations

  1. Department of Microbiology, Immunology and Parasitology UNIFESP Federal University of São Paulo, Sao Paulo, São Paulo, Brazil

    Valquiria Bueno

  2. MRC-ARUK Centre for Musculoskeletal Ageing Research, Institute of Inflammation and Ageing Birmingham University Medical School Birmingham, Birmingham, United Kingdom

    Janet M. Lord

  3. Institute of Inflammation and Ageing, University of Birmingham University of Birmingham Research Laboratories, Birmingham, United Kingdom

    Thomas A. Jackson

Rights and permissions

Reprints and permissions

Copyright information

© 2017 Springer International Publishing Switzerland

About this chapter

Cite this chapter

Tariq, M.A., Hazeldine, J., Lord, J.M. (2017). Innate Immunosenescence and Its Impact on Health in Old Age. In: Bueno, V., Lord, J., Jackson, T. (eds) The Ageing Immune System and Health. Springer, Cham. https://doi.org/10.1007/978-3-319-43365-3_1

Download citation

  • DOI: https://doi.org/10.1007/978-3-319-43365-3_1

  • Published:

  • Publisher Name: Springer, Cham

  • Print ISBN: 978-3-319-43363-9

  • Online ISBN: 978-3-319-43365-3

  • eBook Packages: MedicineMedicine (R0)

Publish with us

Policies and ethics

Search

Navigation