Abstract
Aging or senescence is a complex process that causes the progressive degeneration of physiological capacity, resulting in a greater probability of death. Senescence affects all cells and tissues of organism, including those of the immune system. The immune system of older people declines with age, and this phenomenon is known as immunosenescence. Immunosenescence results in greater susceptibility to pathology of various age-related disorders, a higher incidence of infections, neoplasia and autoimmune diseases, impaired response, susceptibility to chronic diseases, and weak response to vaccination. Aging affects cells of both innate and adaptive immunity. The cells involved in innate immunity show altered functions. Neutrophils, monocytes, or macrophages show reduced phagocytic ability and impaired superoxide production. Macrophages show reduced levels of MHC class II complexes. Dendritic cells show impaired migration and phagocytic capability and natural killer cells, a reduction in cytotoxicity. Mast cell number increases with age, and degranulation changes contribute to inflammatory responses in elderly. Aging characterized by a chronic, low-grade inflammation is termed as “inflammaging.” Inflammaging is a highly significant risk factor for morbidity and mortality in the elderly people. This phase of inflammation is associated with many chronic human diseases, including allergy, arthritis, atherosclerosis, cancer, and autoimmune diseases. Aging can cause dysregulation of the adaptive immune system due to diminished number of naïve B and T cells but a reciprocal rise in memory B and T cells. This results in decrease in T- and B-cell diversity along with low antibody affinity and rise of autoreactive antibodies causing overall weakening of the immune system. An increase in inflammatory markers with age, along with decreased efficacy of immunological surveillance, a process where neoplastic cells are detected and destroyed, increases the risk of cancer with age. Anemia of inflammation (AI), also referred as anemia of chronic disease (ACD), is the most common cause of anemia in the elderly. Oxidative stress may cause erythrocyte damage and thus results into AI. The interplay of inflammation and oxidative stress is described in a number of age-related disorders, such as anemia, cancer, angiogenesis, and vascular diseases.
Access this chapter
Tax calculation will be finalised at checkout
Purchases are for personal use only
References
Kirkwood TB (2011) Growing up in ageing. Clin Med (Lond) 11(2):169–170
Jemal A et al (2010) Cancer statistics, 2010. CA Cancer J Clin 60(5):277–300
Aw D, Silva AB, Palmer DB (2007) Immunosenescence: emerging challenges for an ageing population. Immunology 120(4):435–446
Yoshikawa T, Naito Y (2000) The role of neutrophils and inflammation in gastric mucosal injury. Free Radic Res 33(6):785–794
Baylis D et al (2013) Understanding how we age: insights into inflammaging. Longev Healthspan 2(1):8
Rohrig G (2016) Anemia in the frail, elderly patient. Clin Interv Aging 11:319–326
Franceschi C et al (2000) Inflamm-aging. An evolutionary perspective on immunosenescence. Ann N Y Acad Sci 908:244–254
Boots AM et al (2013) The influence of ageing on the development and management of rheumatoid arthritis. Nat Rev Rheumatol 9(10):604–613
Theurl I et al (2011) Pharmacologic inhibition of hepcidin expression reverses anemia of chronic inflammation in rats. Blood 118(18):4977–4984
Davis BK, Wen H, Ting JP (2011) The inflammasome NLRs in immunity, inflammation, and associated diseases. Annu Rev Immunol 29:707–735
Shayganni E et al (2016) Inflammaging and cardiovascular disease: Management by medicinal plants. Phytomedicine 23(11):1119–1126
Kuek A, Hazleman BL, Ostor AJ (2007) Immune-mediated inflammatory diseases (IMIDs) and biologic therapy: a medical revolution. Postgrad Med J 83(978):251–260
Deleidi M, Jaggle M, Rubino G (2015) Immune aging, dysmetabolism, and inflammation in neurological diseases. Front Neurosci 9:172
Ginaldi L, Di Benedetto MC, De Martinis M (2005) Osteoporosis, inflammation and ageing. Immun Ageing 2:14
Frame B, Nixon RK (1968) Bone-marrow mast cells in osteoporosis of aging. N Engl J Med 279(12):626–630
Prattichizzo F et al (2016) “Inflammaging” as a druggable target: a senescence-associated secretory phenotype-centered view of type 2 diabetes. Oxidative Med Cell Longev 2016:1810327
Salminen A, Kaarniranta K, Kauppinen A (2012) Inflammaging: disturbed interplay between autophagy and inflammasomes. Aging-US 4(3):166–175
Khansari N, Shakiba Y, Mahmoudi M (2009) Chronic inflammation and oxidative stress as a major cause of age-related diseases and cancer. Recent Patents Inflamm Allergy Drug Discov 3(1):73–80
Fibach E, Rachmilewitz E (2008) The role of oxidative stress in hemolytic anemia. Curr Mol Med 8(7):609–619
Reuter S et al (2010) Oxidative stress, inflammation, and cancer: how are they linked? Free Radic Biol Med 49(11):1603–1616
Kim YW, West XZ, Byzova TV (2013) Inflammation and oxidative stress in angiogenesis and vascular disease. J Mol Med (Berl) 91(3):323–328
Tomlinson S (1993) Complement defense mechanisms. Curr Opin Immunol 5(1):83–89
Delves PJ, Roitt IM (2000) The immune system. First of two parts. N Engl J Med 343(1):37–49
Delves PJ, Roitt IM (2000) The immune system. Second of two parts. N Engl J Med 343(2):108–117
Lanier LL (2005) NK cell recognition. Annu Rev Immunol 23:225–274
Mariani E et al (2001) Different IL-8 production by T and NK lymphocytes in elderly subjects. Mech Ageing Dev 122(13):1383–1395
Ogata K et al (1997) Natural killer cells in the late decades of human life. Clin Immunol Immunopathol 84(3):269–275
Gayoso I et al (2011) Immunosenescence of human natural killer cells. J Innate Immun 3(4):337–343
Solana R, Mariani E (2000) NK and NK/T cells in human senescence. Vaccine 18(16):1613–1620
Lutz CT et al (2005) Reciprocal age related change in natural killer cell receptors for MHC class I. Mech Ageing Dev 126(6–7):722–731
Murasko DM, Jiang J (2005) Response of aged mice to primary virus infections. Immunol Rev 205:285–296
Bottino C, Moretta L, Moretta A (2006) NK cell activating receptors and tumor recognition in humans. Curr Top Microbiol Immunol 298:175–182
Bruunsgaard H et al (2001) Decreased natural killer cell activity is associated with atherosclerosis in elderly humans. Exp Gerontol 37(1):127–136
Bruunsgaard H, Pedersen M, Pedersen BK (2001) Aging and proinflammatory cytokines. Curr Opin Hematol 8(3):131–136
Rando TA, Chang HY (2012) Aging, rejuvenation, and epigenetic reprogramming: resetting the aging clock. Cell 148(1–2):46–57
Ziegler DA et al (2010) Cognition in healthy aging is related to regional white matter integrity, but not cortical thickness. Neurobiol Aging 31(11):1912–1926
Zimmermann HW, Trautwein C, Tacke F (2012) Functional role of monocytes and macrophages for the inflammatory response in acute liver injury. Front Physiol 3:56
Ancuta P et al (2009) Transcriptional profiling reveals developmental relationship and distinct biological functions of CD16+ and CD16− monocyte subsets. BMC Genomics 10:403
Maes M (1999) Major depression and activation of the inflammatory response system. Adv Exp Med Biol 461:25–46
Krabbe H (2001) [Experiences with the conversion of legal regulations in practice]. Dtsch Tierarztl Wochenschr 108(8):353–357
Nyugen J et al (2010) Impaired functions of peripheral blood monocyte subpopulations in aged humans. J Clin Immunol 30(6):806–813
Merino A et al (2011) Senescent CD14+CD16+ monocytes exhibit proinflammatory and proatherosclerotic activity. J Immunol 186(3):1809–1815
Hearps AC et al (2012) Aging is associated with chronic innate immune activation and dysregulation of monocyte phenotype and function. Aging Cell 11(5):867–875
Herrero C et al (2002) Immunosenescence of macrophages: reduced MHC class II gene expression. Exp Gerontol 37(2–3):389–394
Zissel G et al (1999) Pharmacological modulation of the IFNgamma-induced accessory function of alveolar macrophages and peripheral blood monocytes. Inflamm Res 48(12):662–668
Zissel G, Schlaak M, Muller-Quernheim J (1999) Age-related decrease in accessory cell function of human alveolar macrophages. J Investig Med 47(1):51–56
Roubenoff R et al (1998) Monocyte cytokine production in an elderly population: effect of age and inflammation. J Gerontol A Biol Sci Med Sci 53(1):M20–M26
Shaw AC et al (2011) Dysregulation of human Toll-like receptor function in aging. Ageing Res Rev 10(3):346–353
Uyemura K, Castle SC, Makinodan T (2002) The frail elderly: role of dendritic cells in the susceptibility of infection. Mech Ageing Dev 123(8):955–962
Frasca D et al (2003) Decreased E12 and/or E47 transcription factor activity in the bone marrow as well as in the spleen of aged mice. J Immunol 170(2):719–726
Frasca D et al (2003) Effects of aging on proliferation and E47 transcription factor activity induced by different stimuli in murine splenic B cells. Mech Ageing Dev 124(4):361–369
Signer RA et al (2008) Aging and cancer resistance in lymphoid progenitors are linked processes conferred by p16Ink4a and Arf. Genes Dev 22(22):3115–3120
Plowden J et al (2004) Innate immunity in aging: impact on macrophage function. Aging Cell 3(4):161–167
Boehmer ED et al (2005) Aging negatively skews macrophage TLR2- and TLR4-mediated pro-inflammatory responses without affecting the IL-2-stimulated pathway. Mech Ageing Dev 126(12):1305–1313
Gomez JA et al (2005) X box-like sequences in the MHC class II region maintain regulatory function. J Immunol 175(2):1030–1040
Fulop T et al (2004) Signal transduction and functional changes in neutrophils with aging. Aging Cell 3(4):217–226
Effros RB (1997) Loss of CD28 expression on T lymphocytes: a marker of replicative senescence. Dev Comp Immunol 21(6):471–478
Weng CY et al (2009) MAP kinase pathway is involved in IGF-1-stimulated proliferation of human retinal pigment epithelial cells (hRPE). Curr Eye Res 34(10):867–876
Larbi A, Blin D, Cyteval C (2011) [Hip and pelvic injuries in the elderly]. J Radiol 92(6):567–580
Petrov M (2013) Nutrition, inflammation, and acute pancreatitis. ISRN Inflamm 2013:341410
Kelsall BL, Strober W (1996) The role of dendritic cells in antigen processing in the Peyer’s patch. Ann N Y Acad Sci 778:47–54
Gunin AG et al (2011) Age-related changes in proliferation, the numbers of mast cells, eosinophils, and cd45-positive cells in human dermis. J Gerontol A Biol Sci Med Sci 66(4):385–392
Burnet M (1959) Auto-immune disease. I. Modern immunological concepts. Br Med J 2(5153):645–650
Frasca D et al (2016) The generation of memory B cells is maintained, but the antibody response is not, in the elderly after repeated influenza immunizations. Vaccine 34(25):2834–2840
Aspinall R, Andrew D (2000) Immunosenescence: potential causes and strategies for reversal. Biochem Soc Trans 28(2):250–254
Linton PJ, Dorshkind K (2004) Age-related changes in lymphocyte development and function. Nat Immunol 5(2):133–139
Aspinall R, Andrew D (2000) Thymic involution in aging. J Clin Immunol 20(4):250–256
Massoud AH et al (2014) Dendritic cell immunoreceptor: a novel receptor for intravenous immunoglobulin mediates induction of regulatory T cells. J Allergy Clin Immunol 133(3):853–63 e5
Steinmann GG (1986) Changes in the human thymus during aging. Curr Top Pathol 75:43–88
Manley NR et al (2011) Structure and function of the thymic microenvironment. Front Biosci (Landmark Ed) 16:2461–2477
Beerman I et al (2010) Stem cells and the aging hematopoietic system. Curr Opin Immunol 22(4):500–506
Goronzy JJ et al (2012) Signaling pathways in aged T cells – a reflection of T cell differentiation, cell senescence and host environment. Semin Immunol 24(5):365–372
Clambey ET et al (2008) Identification of two major types of age-associated CD8 clonal expansions with highly divergent properties. Proc Natl Acad Sci USA 105(35):12997–13002
Strindhall J et al (2007) No Immune Risk Profile among individuals who reach 100 years of age: findings from the Swedish NONA immune longitudinal study. Exp Gerontol 42(8):753–761
Zediak VP, Maillard I, Bhandoola A (2007) Multiple prethymic defects underlie age-related loss of T progenitor competence. Blood 110(4):1161–1167
Dykstra B et al (2011) Clonal analysis reveals multiple functional defects of aged murine hematopoietic stem cells. J Exp Med 208(13):2691–2703
Frasca D, Blomberg BB (2009) Effects of aging on B cell function. Curr Opin Immunol 21(4):425–430
Cancro MP et al (2009) B cells and aging: molecules and mechanisms. Trends Immunol 30(7):313–318
McElhaney JE et al (2012) The unmet need in the elderly: how immunosenescence, CMV infection, co-morbidities and frailty are a challenge for the development of more effective influenza vaccines. Vaccine 30(12):2060–2067
Miller JP, Cancro MP (2007) B cells and aging: balancing the homeostatic equation. Exp Gerontol 42(5):396–399
Ryan GB, Majno G (1977) Acute inflammation. A review. Am J Pathol 86(1):183–276
Weiss U (2008) Inflammation. Nature 454(7203):427
de Zoete MR et al (2014) Inflammasomes. Cold Spring Harb Perspect Biol 6(12):a016287
McIntire CR, Yeretssian G, Saleh M (2009) Inflammasomes in infection and inflammation. Apoptosis 14(4):522–535
Theoharides TC et al (2007) Differential release of mast cell mediators and the pathogenesis of inflammation. Immunol Rev 217:65–78
Bienenstock J et al (1987) Mast cell involvement in various inflammatory processes. Am Rev Respir Dis 135(6 Pt 2):S5–S8
Gabay C (2006) Interleukin-6 and chronic inflammation. Arthritis Res Ther 8(Suppl 2):S3
Tang C et al (2012) Interleukin-23: as a drug target for autoimmune inflammatory diseases. Immunology 135(2):112–124
Sternberg EM (2001) Neuroendocrine regulation of autoimmune/inflammatory disease. J Endocrinol 169(3):429–435
Rodier F, Campisi J (2011) Four faces of cellular senescence. J Cell Biol 192(4):547–556
Dall’Olio F et al (2013) N-glycomic biomarkers of biological aging and longevity: a link with inflammaging. Ageing Res Rev 12(2):685–698
Biagi E et al (2011) The aging gut microbiota: new perspectives. Ageing Res Rev 10(4):428–429
Franceschi C, Bonafe M, Valensin S (2000) Human immunosenescence: the prevailing of innate immunity, the failing of clonotypic immunity, and the filling of immunological space. Vaccine 18(16):1717–1720
Franceschi C, Campisi J (2014) Chronic inflammation (inflammaging) and its potential contribution to age-associated diseases. J Gerontol A Biol Sci Med Sci 69(Suppl 1):S4–S9
Williams CMM, Galli SJ (2000) Mast cells can amplify airway reactivity and features of chronic inflammation in an asthma model in mice. J Exp Med 192(3):455–462
Bischoff SC (2007) Role of mast cells in allergic and non-allergic immune responses: comparison of human and murine data. Nat Rev Immunol 7(2):93–104
Caughey GH (2007) Mast cell tryptases and chymases in inflammation and host defense. Immunol Rev 217:141–154
Crivellato E et al (2004) The mast cell: an active participant or an innocent bystander? Histol Histopathol 19(1):259–270
Nguyen M, Pace AJ, Koller BH (2005) Age-induced reprogramming of mast cell degranulation. J Immunol 175(9):5701–5707
Petrov VV et al (2013) [Age-related changes in mast cells and eosinophils of human dermis]. Ontogenez 44(3):179–185
Kelsall MA (1966) Aging on mast cells and plasmacytes in the brain of hamsters. Anat Rec 154(4):727–739
Yang-lin Hua WG, Li H-y, Tang J (2016) The role of the mast cell in skin aging. J Dermatol Res Ther 2(5):035
Grizzi F et al (2013) Mast cells and the liver aging process. Immun Ageing 10(1):9
Abshire TC (1996) The anemia of inflammation. A common cause of childhood anemia. Pediatr Clin North Am 43(3):623–637
Roy CN (2010) Anemia of inflammation. Hematology Am Soc Hematol Educ Program 2010:276–280
Saxena RK, Khandelwal S (2009) Aging and destruction of blood erythrocytes in mice. Curr Sci 97(4):500–507
Fraenkel PG (2017) Anemia of inflammation: a review. Med Clin North Am 101(2):285–296
Roy A, Sil PC (2012) Tertiary butyl hydroperoxide induced oxidative damage in mice erythrocytes: Protection by taurine. Pathophysiology 19(2):137–148
He C, Klionsky DJ (2009) Regulation mechanisms and signaling pathways of autophagy. Annu Rev Genet 43:67–93
Artz AS et al (2014) Unexplained anaemia in the elderly is characterised by features of low grade inflammation. Br J Haematol 167(2):286–289
Akohoue SA et al (2007) Energy expenditure, inflammation, and oxidative stress in steady-state adolescents with sickle cell anemia. Pediatr Res 61(2):233–238
Pandey KB, Rizvi SI (2011) Biomarkers of oxidative stress in red blood cells. Biomed Pap Med Fac Univ Palacky Olomouc Czech Repub 155(2):131–136
Puri N, Roche PA (2008) Mast cells possess distinct secretory granule subsets whose exocytosis is regulated by different SNARE isoforms. Proc Natl Acad Sci USA 105(7):2580–2585
Malaviya R, Abraham SN (2001) Mast cell modulation of immune responses to bacteria. Immunol Rev 179:16–24
Madewell BR, Munn RJ, Phillips LP (1987) Endocytosis of erythrocytes in vivo and particulate substances in vitro by feline neoplastic mast cells. Can J Vet Res 51(4):517–520
Spicer SS, Simson JA, Farrington JE (1975) Mast cell phagocytosis of red blood cells. Am J Pathol 80(3):481–498
Naqvi N et al (2017) Role of Mast Cells in clearance of Leishmania through extracellular trap formation. Sci Rep 7(1):13240
Sharma P, Puri N (2018) A new role for mast cells as scavengers for clearance of erythrocytes damaged due to oxidative stress. Immunol Lett 199:23–35
Ultmann JE et al (1964) Clinical, cytologic, and biochemical studies in systemic mast cell disease. Ann Intern Med 61:326–333
Lim KH et al (2009) Systemic mastocytosis in 342 consecutive adults: survival studies and prognostic factors. Blood 113(23):5727–5736
Vincent L et al (2013) Mast cell activation contributes to sickle cell pathobiology and pain in mice. Blood 122(11):1853–1862
Kilari D, Mohile SG (2012) Management of cancer in the older adult. Clin Geriatr Med 28(1):33–49
Zbar AP, Gravitz A, Audisio RA (2012) Principles of surgical oncology in the elderly. Clin Geriatr Med 28(1):51–71
DePinho RA (2000) The age of cancer. Nature 408(6809):248–254
Hoffe S, Balducci L (2012) Cancer and age: general considerations. Clin Geriatr Med 28(1):1–18
Balducci L (2005) Epidemiology of cancer and aging. J Oncol Manag 14(2):47–50
Balducci L (2005) Prevention of cancer in the older person. Cancer J 11(6):442–448
Balducci L (2005) The nexus of cancer and age. Discov Med 5(30):516–519
Balducci L, Aapro M (2005) Epidemiology of cancer and aging. Cancer Treat Res 124:1–15
Balducci L, Ershler WB (2005) Cancer and ageing: a nexus at several levels. Nat Rev Cancer 5(8):655–662
Pavlidis N, Stanta G, Audisio RA (2012) Cancer prevalence and mortality in centenarians: a systematic review. Crit Rev Oncol Hematol 83(1):145–152
Baade PD et al (2012) Factors associated with diagnostic and treatment intervals for prostate cancer in Queensland, Australia: a large cohort study. Cancer Causes Control 23(4):625–634
Baade PD et al (2012) Estimating the future burden of cancers preventable by better diet and physical activity in Australia. Med J Aust 196(5):337–340
Pavlidis N et al (2012) Long-term survivors among patients with cancer of unknown primary. Crit Rev Oncol Hematol 84(1):85–92
Author information
Authors and Affiliations
Corresponding author
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 2019 Springer Nature Singapore Pte Ltd.
About this chapter
Cite this chapter
Paudel, S., Sharma, P., Puri, N. (2019). Immunosenescence, Inflammaging, and Their Implications for Cancer and Anemia. In: Rath, P. (eds) Models, Molecules and Mechanisms in Biogerontology. Springer, Singapore. https://doi.org/10.1007/978-981-13-3585-3_14
Download citation
DOI: https://doi.org/10.1007/978-981-13-3585-3_14
Published:
Publisher Name: Springer, Singapore
Print ISBN: 978-981-13-3584-6
Online ISBN: 978-981-13-3585-3
eBook Packages: Biomedical and Life SciencesBiomedical and Life Sciences (R0)