Hostname: page-component-669899f699-7tmb6 Total loading time: 0 Render date: 2025-04-25T08:06:28.960Z Has data issue: false hasContentIssue false
  • English
  • Français

Review on immunosenescence

Part of: Bespoke shallow archive Weizmann

Published online by Cambridge University Press:  01 August 2007

Lia Ginaldi ,
Lucia Paola Mengoli  and
Massimo De Martinis
Lia Ginaldi*
Affiliation:
Department of Internal Medicine and Public Health, L'Aquila University, Italy
Lucia Paola Mengoli
Affiliation:
Department of Internal Medicine and Public Health, L'Aquila University, Italy
Massimo De Martinis
Affiliation:
Department of Internal Medicine and Public Health, L'Aquila University, Italy
*
Address for correspondence: Professor Lia Ginaldi, Dept. of Internal Medicine & Public Health, University of L'Aquila, Via Vetoio – Coppito, 67100 L'Aquila, ITALY
Get access Rights & Permissions [Opens in a new window]

Extract

The improvements of socio-environmental conditions, medical care and quality of life have caused a general improvement in the health status of the population and a consequent reduction of morbidity and mortality, resulting in an overall increased life-expectancy. The role of immunosenescence was negligible in the past, when the human lifespan was 40–50 years, and its impact on morbidity and mortality has emerged in combination with the extension of lifespan. Immunosenescence results from multifactorial processes that act on all components of the immune system. The changes associated with immunosenescence are playing an increasingly important role in the emergence of a series of age-related pathologies, conditioning the present epidemiology of old people.

Type
Biological gerontology
Information
Reviews in Clinical Gerontology , Volume 17 , Issue 3 , August 2007 , pp. 161 - 169
Copyright
Copyright © Cambridge University Press 2008

Access options

Get access to the full version of this content by using one of the access options below. (Log in options will check for institutional or personal access. Content may require purchase if you do not have access.)

Article purchase

Temporarily unavailable

References

1Burkle, A, Caselli, G, Franceschi, C et al. Pathophysiology of ageing, longevity and age-related diseases. Immun Ageing 2007; 4:1–8.CrossRefGoogle ScholarPubMed
2The Italian Multicentric Study on Centenarians. Epidemiological and socioeconomic aspects of Italian centenarians. Arch Gerontol Geriat 1997; 25:149–57.CrossRefGoogle Scholar
3De Martinis, M, Franceschi, C, Monti, D, Ginaldi, L. Inflamm-ageing and lifelong antigenic load as major determinants of ageing rate and longevity. Febs Lett 2005; 579:2035–39.CrossRefGoogle ScholarPubMed
4Vasto, S, Candore, G, Balistreri, CR et al. Inflammatory networks in ageing, age-related diseases and longevity. Mech Ageing Dev 2007; 128:83–91.CrossRefGoogle ScholarPubMed
5Cappola, AR, Xue, Q-L, Ferrucci, L, Guralnik, JM, Volpato, S, Fried, LP. Insulin-like growth factor I and interleukin-6 contribute synergistically to disability and mortality in older women. J Clin Endocrinol Metab 2003; 88:2019–25.CrossRefGoogle ScholarPubMed
6Troen, BR. The biology of aging. Mt Sinai J Med 2003; 70:3–22.Google ScholarPubMed
7Hughes, KA, Alipaz, JA, Drnevich, JM, Reynolds, RM. A test of evolutionary theories of aging. Proc Natl Acad Sci 2002; 99:14286–91.CrossRefGoogle ScholarPubMed
8Rea, IM. Ageing in the 21st century. Where to and how will we get there? Report on the 10th congress of the International Association of Biomedical Gerontology, the geriatrician's view. Exp Gerontol 2004; 39:283–84.CrossRefGoogle ScholarPubMed
9Ginaldi, L, Sternberg, H. The immune system. In: Timiras, PS ed. Physiological basis of aging and geriatrics, fourth edition. Place? LLC Press, State ? USA, 2007; Chapter 14:231–48.Google Scholar
10De Martinis, M, Franceschi, C, Monti, D, Ginaldi, L. Inflammation markers predicting frailty and mortality in the elderly. Exp Mol Pathol 2006; 80:219–27.CrossRefGoogle ScholarPubMed
11Franceschi, C, Capri, M, Monti, D et al. Inflammaging and anti-inflammaging: A systemic perspective on aging and longevity emerged from studies in humans. Mech Ageing Dev 2007; 128:92–105.CrossRefGoogle ScholarPubMed
12Franceschi, C, Valensin, S, Fagnoni, F, Barbi, C, Bonafè, M. Biomarkers of immunosenescence within an evolutionary perspective: the challenge of heterogeneity and the role of antigenic load. Exp Gerontol 1999; 34:911–21.CrossRefGoogle ScholarPubMed
13Appay, V, Almeida, JR, Sauce, D, Autran, B, Papagno, L. Accelerated immune senescence and HIV-1 infection. Exp Gerontol 2007; 42:432–37.CrossRefGoogle ScholarPubMed
14Goronzy, JJ, Fujii, H, Weyand, CM. Telomeres immune aging and autoimmunity. Exp Gerontol 2006; 41:246–51.CrossRefGoogle ScholarPubMed
15Witkowski, JM, Soroczynska-Cybula, M, Bryl, E, Smolenska, Z, Jozwik, A. Klotho-a common link in physiological and rheumatoid arthritis-related aging of human CD4+ lymphocytes. J Immunol 2007; 178:771–77.CrossRefGoogle ScholarPubMed
16Pawelec, G, Koch, S, Guessmann, H et al. Immunosenescence, suppression and tumour progression. Cancer Immunol Immunother 2006; 55:981–86.CrossRefGoogle ScholarPubMed
17Pawelec, G., Larbi A. Immunity and ageing in man: Annual Review 2006/2007. Exp Gerontol 2008; 43:34–38.Google ScholarPubMed
18Effros, RB, Dagarag, M, Valenzuela, HF. In vitro senescence of immune cells. Exp Gerontol 2003; 38:1243–49.CrossRefGoogle ScholarPubMed
19Thewissen, M, Somers, V, Venken, K et al. Analyses of immunosenescent markers in patients with autoimmune disease. Clin Immunol 2007; 123:209–18.CrossRefGoogle ScholarPubMed
20Effros, RB. Telomerase induction in T cells: a cure for aging and disease? Exp Gerontol 2007; 42:416–20.CrossRefGoogle Scholar
21Koch, S, Solona, R, De la Rosa, O, Pawelec, G. Human cytomegalovirus infection and T-cell immunosenescence: a mini review. Mech Ageing Dev 2006; 127:538–43.CrossRefGoogle ScholarPubMed
22Vukmanovic-Stejic, M, Zhang, Y, CooK, JE et al. Human CD4 +CD25hi Foxp3+ regulatory T cells are derived by rapid turnover of memory populations in vivo. J Clin Invest 2006; 116:2423–33.CrossRefGoogle ScholarPubMed
23Wolf, D, Rumpold, H, Koppelstatter, C et al. Telomere length of in vivo expended CD4+ CD25+ regulatory T-cells is preserved in cancer patients. Cancer Immunol Immunother 2006; 55:1198–2008.CrossRefGoogle Scholar
24Ouyang, Q, Wagner, WM, Wikby, A et al. Large numbers of dysfunctional CD8+ T lymphocytes bearing receptors for a single dominant CMV epitope in the very old. J Clin Immunol 2003; 23:247–57.CrossRefGoogle ScholarPubMed
25Franceschi, C, Bonafè, M, Valensin, S. Human immunosenescence: the prevailing of innate immunity, the failing of clonotypic immunity, and the filling of immunological space. Vaccine 2000; 18:1717–20.CrossRefGoogle ScholarPubMed
26Ouyang, Q, Wagner, WM, Voehringer, D et al. Age-associated accumulation of CMV-specific CD8+ T cells expressing the inhibitory killer-cell lectin-like receptor G1 (KLRG1). Exp Gerontol 2003; 38:911–20.CrossRefGoogle ScholarPubMed
27Wenberger, B, Lazuardi, L, Weiskirchner, I et al. Healthy aging and latent infection with CMV lead to distinct changes in CD8+ and CD4+ T-cell subsets in the elderly. Hum Immunol 2007; 68:86–90.CrossRefGoogle Scholar
28Pourgheysori, B, Khan, N, Best, D, Bruton, R, Nayak, L, Moss, PA. The cytomegalovirus-specific CD4+ T-cell response expands with age and markedly alters the CD4+ T-cell repertoire. J Virol 2007; 81:7759–65.CrossRefGoogle Scholar
29Van Leeuwen, EM, Koning, JJ, Remmerswaal, EB, van Boarle, D, van Lier, RA, ten Berge, IJ. Differential usage of cellular niches by cytomegalovirus versus EBV-and influenza virus-specific CD8+ T cells. J Immunol 2006; 177:4998–5005.CrossRefGoogle ScholarPubMed
30Zhang, X, Fujii, H, Kishimoto, H, LeRoy, E, Surh, CD, Sprent, J. Aging leads to disturbed homeostasis of memory phenotype CD8+ cells. J Exp Med 2002; 195:283–93.CrossRefGoogle ScholarPubMed
31Schmaltz, HN, Fried, LP, Xue, QL et al. Chronic cytomegalovirus infection and inflammation are associated with prevalent frailty in community-dwelling older women. J Am Geriatr Soc 2005; 53:747–54.CrossRefGoogle ScholarPubMed
32Wikby, A, Nilsson, BO, Forsey, R et al. The immune risk phenotype is associated with IL-6 in the terminal decline stage: findings from the Swedish NONA immune longitudinal study of very late-life functioning. Mech Ageing Dev 2006; 127:695–04.CrossRefGoogle ScholarPubMed
33Hadrup, SR, Kollgard, T, Saremet, T et al. Longitudinal studies of clonally expanded CD8 T cells reveal a repertoire shrinkage predicting mortality and an increased number of dysfunctional cytomegalovirus-specific T cells in the very elderly. J Immunol 2006; 176:2645–53.CrossRefGoogle Scholar
34Hollegaard, MV, Bidwell, JL. Cytokine gene polymer phism in human disease: on-line databases.Genes Immun 2006; S37:269–76.CrossRefGoogle Scholar
35Licastro, F, Candore, G, Lio, D et al. Innate immunity and inflammation in ageing: a key for understanding age-related diseases. Immun Ageing 2005; 2:8–13.CrossRefGoogle ScholarPubMed
36Bonafè, M, Olivieri, F, Cavallone, L et al. A gender-dependent genetic predisposition to produce high levels of IL-6 is detrimental for longevity. Eur J Immunol 2001; 31:2357–61.3.0.CO;2-X>CrossRefGoogle ScholarPubMed
37Olivieri, F, Bonafè, M, Giovagnetti, S et al. In vitro IL-6 production by EBV-immortalized B lymphocytes from young and elderly people genotyped for –174 C/G polymorphism in IL-6 gene: a model to study the genetic basis of inflamm-aging. Mech Ageing Dev 2003; 124:549–53.CrossRefGoogle Scholar
38Bruunsgaard, H, Andersen-Ramberg, K, Jeune, B et al. A high plasma concentration of TNF-α is associated with dementia in centenarians. J Gerontol 1999; 54:357–64.CrossRefGoogle ScholarPubMed
39Franceschi, C, Olivieri, F, Marchegiani, F et al. Genes involved in immune response/inflammation, IGF1/insulin pathway and response to oxidative stress play a major role in the genetics of human longevity: the lesson of centenarians. Mech Ageing Dev 2005; 126:351–61.CrossRefGoogle Scholar
40Mannucci, PM, Mari, D, Merati, G et al. Gene polymorphisms predicting high plasma levels of coagulation and fibrinolysis proteins. A study in centenarians. Arterioscler Thromb Vasc Biol 1997; 17:755–59.CrossRefGoogle ScholarPubMed
41Coppola, R, Mari, D, Lattuada, A, Franceschi, C. Von Willebrand factor in Italian centenarians. Hematologica 2003; 88:39–43.Google ScholarPubMed
42Lio, D, Scola, L, Crivello, A et al. Inflammation, genetics, and longevity: further studies on the protective effects in men of IL-10-1082 promoter SNP and its interaction with TNF-a-308 promoter SNP. J Med Genet 2002; 39:1–3.Google Scholar
43Mariani, E, Pulsatelli, L, Neri, S et al. RANTES and MIP-1alpha production by T lymphocytes, monocytes and NK cells from nonagenarian subjects. Exp Gerontol 2002; 37:219–26.CrossRefGoogle Scholar
44Conboy, IM, Randi, TA. Aging, stem cells and tissue regeneration: lesson from muscle. Cell Cycle 2005; 4:407–10.CrossRefGoogle ScholarPubMed
45Conboy, IM, Conboy, MJ, Wagers, AJ et al. Rejuvention of aged progenitor cells by exposure to a young systemic environment. Nature 2005; 433:760–64.CrossRefGoogle ScholarPubMed
46Bagnara, GP, Bonsi, L, Strippoli, P et al. Hemopoiesis in healthy old people and centenarians: well-maintained responsiveness of CD34 +cells to hemopoietic growth factors and remodeling of cytokine network. J Gerontol 2000; 55:61–66.Google ScholarPubMed
47Moresi, R, Tesei, S, Costarelli, L et al. Age- and gender-related alterations of the number and clonogenic capacity of circulating CD34 + progenitor cells. Biogerontology 2005; 6:185–92.CrossRefGoogle ScholarPubMed
48Candore, G, Colonna-Romano, G, Balistreri, CR et al. Biology of longevity: role of the innate immune system. Rejuvenation Res 2006; 9:143–48.CrossRefGoogle ScholarPubMed
49Bonafe, M, Salvioli, B, Barbi, C et al. The different apoptotic potential of the p53 codon 72 alleles increases with age and modulates in vivo ischaemia-induced cell death. Cell Death Differ 2004; 11:962–73.CrossRefGoogle ScholarPubMed
50Salvioli, S, Bonafe, M, Barbi, C et al. P53 codon 72 alleles influence the response to anticancer drugs in cells from aged people by regulating the cell cycle inhibitor p21 WAF1. Cell Cycle 2005; 4:1264–71.CrossRefGoogle Scholar
51Bonafe, M, Olivieri, F, Cavallone, L et al. A gender-dependent genetic predisposition to produce high levels of IL-6 is detrimental for longevity. Eur J Immunol 2001; 31:2357–61.3.0.CO;2-X>CrossRefGoogle ScholarPubMed
52Bonfigli, AR, Scrollo, C, Cenerelli, S et al. Plasminogen activator inhibitor-1 plasma level increases with age in subjects with the 4G allele at position-675 in the promoter region. Thromb Haemost 2004; 92:1164–65.Google ScholarPubMed
53Cipriano, C, Caruso, C, Lio, D et al. The 308 G/A polymorphism of TNF-α influences immunological parameters in old subjects affected by infectious diseases. Int J Immunigenet 2005; 32:13–18.CrossRefGoogle Scholar
54Franceschi, C, Valensin, S, Lescai, F et al. Neuroinflammation and the genetics of Alzheimer's disease: the search for a proinflammatory phenotype. Aging Clin Exp Res 2001; 13:163–70.CrossRefGoogle Scholar
55Szmitko, PE, Wang, C-H, Weisel, RD, de Almeida, JR, Anderson, TJ, Verma, S. New markers of inflammation and endothelial cell activation. Circulation 2003; 108:1917–23.CrossRefGoogle Scholar
56Passeri, G, Pini, G, Troiano, L et al. Low vitamin D status, high bone turnover, and bone fractures in centenarians. J Clin Endocrinol Metab 2003; 88:5109–15.CrossRefGoogle ScholarPubMed
57Roubenoff, R. Catabolism of aging: is it an inflammatory process? Curr Opin Clin Nutr Metab Care 2003; 6:295–99.CrossRefGoogle ScholarPubMed
58Barbieri, M, Ferrucci, L, Ragno, E et al. Chronic inflammation and the effect of IGF-I on muscle strength and power in older persons. Am J Physiol Endocrinol Metab 2003; 284:481–87.CrossRefGoogle ScholarPubMed
59Licastro, F, Grimaldi, LME, Bonafè, M et al. Interleukin-6 gene alleles affect the risk of Alzheimer's disease and levels of the cytokine in blood and brain. Neurobiol Aging 2003; 5831:1–6.Google Scholar
60Abbatecola, AM, Ferrucci, L, Grella, R et al. Diverse effect of inflammatory markers on insulin resistance and insulin-resistance syndrome in the elderly. J Am Geriatr Soc 2004; 52:399–404.CrossRefGoogle ScholarPubMed
61Olsson, J, Wikby, A, Johansson, B, Lofgren, S, Nilsson, BO, Ferguson, FG. 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 2000; 121:187–201.CrossRefGoogle ScholarPubMed
62Wikby, A, Johansson, B, Olsson, J, Lofgren, S, Nilsson, BO, Ferguson, F. Expansions of peripheral blood CD8 T-lymphocyte subpopulations and an association with cytomegalovirus seropositivity in the elderly: the Swedish NONA immune study. Exp Gerontol 2002; 37:445–53.CrossRefGoogle Scholar
63Caruso, C, Lio, D, Cavallone, L, Franceshi, C. Aging, longevity, inflammation and cancer. Ann NY Acad Sci 2004; 1028:1–13.CrossRefGoogle ScholarPubMed
64Balkwill, F, Mantovani, A. Inflammation and cancer: back to Virchow? Lancet 2001; 357:539–45.CrossRefGoogle ScholarPubMed
65Ginaldi, L, Di Benedetto, MC, De Martinis, M. Osteoporosis inflammation and ageing. Immun Ageing 2005; 4:2–14.Google Scholar
66Ginaldi, L, De Martinis, M, Monti, D, Franceschi, C. Chronic antigenic load and apoptosis in immunosenescence. Trends Immunol 2005; 26:79–84.CrossRefGoogle ScholarPubMed
67Capri, M, Monti, D, Salvioli, S et al. Complexity of anti-immunosenescence strategies in humans. Artif Organs 2006; 30:730–42.CrossRefGoogle ScholarPubMed
68Ginaldi, L, De Martinis, M, Modesti, M et al. Immunophenotypical changes of T lymphocytes in the elderly. Gerontology 2000; 46:242–48.CrossRefGoogle ScholarPubMed
69Andrew, D, Aspinall, R. IL-7 and not stem-cell factor reverses both the increase in apoptosis and the decline in thymopoiesis seen in aged mice. J Immunol 2001; 166:1524–30.CrossRefGoogle Scholar
70Zhu, X, Gui, J, Dohkan, J, Cheng, L, Barnes PF, Su DM. Lymphohematopoietic progenitors do not have a synchronized defect with age-related thymic involution. Aging Cell 2007; 6:663–72.CrossRefGoogle Scholar
71Fagnoni, FF, Vescovini, R, Passeri, G et al. Shortage of circulating naive CD8+ T cells provides new insights on immunodeficiency in aging. Blood 2000; 95:2860–8.CrossRefGoogle ScholarPubMed
72Ginaldi, L, De Martinis, M, D'Ostilio, A et al. Changes in the expression of surface receptors on lymphocyte subsets in the elderly: quantitative flow cytometryc analysis. Am J Hematol 2001; 67:63–72.CrossRefGoogle Scholar
73Campisi, J. Cellular senescence and apoptosis: how cellular responses might influence aging phenotypes. Exp Gerontol 2003; 38:5–11.CrossRefGoogle ScholarPubMed
74De Martinis, M, Franceschi, C, Monti, D, Ginaldi, L. Apoptosis remodeling in immunosenescence: implications for strategies to delay ageing. Curr Med Chem 2007; 14:1389–97.CrossRefGoogle ScholarPubMed
75Hayflick, L. Living forever and dying in the attempt. Exp Gerontol 2003; 38:1231–41.CrossRefGoogle ScholarPubMed
76Effros, RB. Replicative senescence of CD8 T cells: effect on human ageing. Exp Gerontol 2004; 39:517–24.CrossRefGoogle ScholarPubMed
77Ginaldi, L, De Martinis, M, Monti, D, Franceschi, C. The immune system in the elderly. Activation-induced and damage-induced apoptosis. Immunol Res 2004; 30:81–94.CrossRefGoogle ScholarPubMed
78Monti, D, Salvioli, S, Capri, M et al. Decreased susceptibility to oxidative stress-induced apoptosis of peripheral blood mononuclear cells from healthy elderly and centenarians. Mech Ageing Dev 2000; 121:239–50.CrossRefGoogle ScholarPubMed
79Gupta, S. Tumor necrosis factor-A-induced apoptosis in T cells from aged humans: a role of TNFR-I and downstream signaling molecules. Exp Gerontol 2002; 37:293–99.CrossRefGoogle Scholar
80De Martinis, M, Modesti, M, Ginaldi, L. Phenotypic and functional changes of circulating monocytes and polymorphonuclear leucocytes from elderly persons. Immunol Cell Biol 2004; 82:415–20.CrossRefGoogle ScholarPubMed
81Larbi, A, Dupuis, G, Khalil, A, Douziech, N, Fortin, C, Fulip, T. Differential role of lipid rafts in the function of CD4 +and CD8+ human T lymphocytes with aging. Cell Signal 2006; 18:1017–30.CrossRefGoogle Scholar
82Franceschi, C, Bonafe, M. Centenaries as a model for healthy aging. Biochem Soc Trans 2003; 31:457–61.CrossRefGoogle Scholar
83Cooper, RS. Gene-environment interactions and the etiology of common complex disease. Ann Int Med 2003; 139:445–49.CrossRefGoogle ScholarPubMed