Skip to main content

Advertisement

SpringerLink
Log in

Inflammation, genetic background and longevity

  • SI: Frailty, Ageing and Inflammation
  • Published:
Biogerontology Aims and scope Submit manuscript

Abstract

Ageing is an inexorable intrinsic process that affects all cells, tissues, organs and individuals. Due to a diminished homeostasis and increased organism frailty, ageing causes a reduction of the response to environmental stimuli and, in general, is associated to an increased predisposition to illness and death. Actually, it is characterized by a state of reduced ability to maintain health and general homeodynamics of the organism. A large part of the ageing phenotype is explained by an imbalance between inflammatory and anti-inflammatory networks, which results in the low grade chronic pro-inflammatory status of ageing, “inflamm-ageing”. It is strictly linked to immunosenescence, and on the whole they are the major contributory factors to the increased frequency of morbidity and mortality among elderly. Inflamm-ageing is compatible with longevity; even if centenarians have an increased level of inflammatory mediators in comparison to old subjects and they are very frail, they also have high level of anti-inflammatory cytokines together with protective genotypes. Actually, data on case control studies performed in Italian centenarians suggest that a pro-inflammatory genotype is unfavourable to reach extreme longevity in good health and likely favours the onset of age-related diseases such as cardiovascular diseases and Alzheimer’s disease, the leading causes of mortality and disability in the elderly. However, many associations between gene variants and longevity have been found only in Italian population. This should not be unexpected, since ageing and longevity are complex traits resulting not only and not exclusively from genetics, but rather from the interactions between genetics, environment and chance.

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

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  • Alonso-Fernández P, Puerto M, Maté I, Ribera JM, de la Fuente M (2008) Neutrophils of centenarians show function levels similar to those of young adults. J Am Geriatr Soc 56:2244–2251

    Article  PubMed  Google Scholar 

  • Balistreri CR, Candore G, Caruso M, Incalcaterra E, Franceschi C, Caruso C (2008) Role of polymorphisms of CC-chemokine receptor-5 gene in acute myocardial infarction and biological implications for longevity. Haematologica 93:637–638

    Article  CAS  PubMed  Google Scholar 

  • Candore G, Balistreri CR, Grimaldi MP, Listì F, Vasto S, Caruso M et al (2006) Opposite role of pro-inflammatory alleles in acute myocardial infarction and longevity: results of studies performed in a Sicilian population. Ann N Y Acad Sci 1067:270–275

    Article  CAS  PubMed  Google Scholar 

  • Candore G, Balistreri CR, Caruso M, Grimaldi MP, Incalcaterra E, Listì F et al (2007) Pharmacogenomics: a tool to prevent and cure coronary heart disease. Curr Pharm Des 13:3726–3734

    Article  CAS  PubMed  Google Scholar 

  • Candore G, Balistreri CR, Bulati M, Colonna-Romano G, Di Bona D, Forte GI et al (2009) Immune-inflammatory responses in successful and unsuccessful ageing. G Gerontol 57:145–152

    Google Scholar 

  • Candore G, Caruso C, Jirillo E, Magrone T, Vasto S (2010a) Low grade inflammation as a common pathogenetic denominator in age-related diseases: novel drug targets for anti-ageing strategies and successful ageing achievement. Current Pharm Des 16:584–596

    Article  CAS  Google Scholar 

  • Candore G, Bulati M, Caruso C, Castiglia L, Colonna-Romano G, Di Bona D et al (2010b) Inflammation, cytokines, immune response, apolipoprotein E, cholesterol, and oxidative stress in Alzheimer disease: therapeutic implications. Rejuvenation Res 13:301–313

    Article  CAS  PubMed  Google Scholar 

  • Capri M, Salvioli S, Monti D, Caruso C, Candore G, Vasto S et al (2008) Human longevity within an evolutionary perspective: the peculiar paradigm of a post-reproductive genetics. Exp Gerontol 43:53–60

    Article  PubMed  Google Scholar 

  • Caruso C, Candore G, Colonna-Romano G, Lio D, Franceschi C (2005) Inflammation and life-span. Science 307:208–209

    Article  CAS  PubMed  Google Scholar 

  • Cevenini E, Caruso C, Candore G, Capri M, Nuzzo D, Duro G et al (2010) Age-related inflammation: the contribution of different organs, tissues and systems. How to face it for therapeutic approaches. Current Pharm Des 16:609–618

    Article  CAS  Google Scholar 

  • Chan OT, Madaio MP, Shlomchik MJ (1999) The central and multiple roles of B cells in lupus pathogenesis. Immunol Rev 169:107–121

    Article  CAS  PubMed  Google Scholar 

  • Chung HY, Cesari M, Anton S, Marzetti E, Giovannini S, Seo AY et al (2009) Molecular inflammation: underpinnings of aging and age-related diseases. Ageing Res Rev 8:18–30

    Article  CAS  PubMed  Google Scholar 

  • Colonna-Romano G, Bulati M, Aquino A, Vitello S, Lio D, Candore G et al (2008) B cell immunosenescence in elderly and centenarians. Rejuvenation Res 11:433–439

    Article  CAS  PubMed  Google Scholar 

  • Colonna-Romano G, Bulati M, Aquino A, Pellicanò M, Vitello S, Lio D et al (2009) A double-negative (IgD−CD27−) B cell population is increased in the peripheral blood of elderly people. Mech Ageing Dev 130:681–690

    Article  CAS  PubMed  Google Scholar 

  • Colonna-Romano G, Buffa S, Bulati M, Candore G, Vaso S, Lio D et al (2010) B cells compartment in centenarian offspring and old people. Current Pharm Des 16:604–608

    Article  CAS  Google Scholar 

  • De la Fuente M, Hernanz A, Vallejo MC (2005) The immune system in the oxidative stress conditions of aging and hypertension: favorable effects of antioxidants and physical exercise. Antioxid Redox Signal 7:1356–1366

    Article  Google Scholar 

  • De Martinis M, Franceschi C, Monti D, Ginaldi L (2005) Inflamm-ageing and lifelong antigenic load as major determinants of ageing rate and longevity. FEBS Lett 579:2035–2039

    Article  PubMed  Google Scholar 

  • Di Bona D, Vasto S, Capurso C, Christiansen L, Deiana L, Franceschi C et al (2009) Effect of interleukin-6 polymorphisms on human longevity: a systematic review and meta-analysis. Ageing Res Rev 8:36–42

    Article  PubMed  Google Scholar 

  • Di Lorenzo G, Balistreri CR, Candore G, Cigna D, Colombo A, Romano GC et al (1999) Granulocyte and natural killer activity in the elderly. Mech Ageing Dev 108:25–38

    Article  CAS  PubMed  Google Scholar 

  • Finch CE, Crimmins EM (2004) Inflammatory exposure and historical changes in human life-spans. Science 305:1736–1739

    Article  CAS  PubMed  Google Scholar 

  • Franceschi C, Monti D, Sansoni P, Cossarizza A (1995) The immunology of exceptional individuals: the lesson of centenarians. Immunol Today 16:12–16

    Article  CAS  PubMed  Google Scholar 

  • 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 18:1717–1720

    Article  CAS  PubMed  Google Scholar 

  • Franceschi C, Capri M, Monti D, Giunta S, Olivieri F, Sevini F et al (2007) Inflammaging and anti-inflammaging: a systemic perspective on aging and longevità emerged from studies in humans. Mech Ageing Dev 128:92–105

    Article  CAS  PubMed  Google Scholar 

  • Franceschi C, Motta L, Motta M, Malaguarnera M, Capri M, Vasto S et al (2008) The extreme longevity: the state of the art in Italy. Exp Gerontol 43:45–52

    Article  PubMed  Google Scholar 

  • Gibson KL, Wu YC, Barnett Y, Duggan O, Vaughan R, Kondeatis E et al (2009) B-cell diversity decreases in old age and is correlated with poor health status. Aging Cell 8:18–25

    Article  CAS  PubMed  Google Scholar 

  • Goto M (2008) Inflammaging (inflammation + aging): a driving force for human aging based on an evolutionarily antagonistic pleiotropy theory? Biosci Trends 2:218–230

    PubMed  Google Scholar 

  • Grubeck-Loebenstein B, Della Bella S, Iorio AM, Michel JP, Pawelec G, Solana R (2009) Immunosenescence and vaccine failure in the elderly. Aging Clin Exp Res 21:201–209

    CAS  PubMed  Google Scholar 

  • Gupta S, Su H, Bi R, Agrawal S, Gollapudi S (2005) Life and death of lymphocytes: a role in immunosenescence. Immun Ageing 2:2

    Article  Google Scholar 

  • Harris DP, Haynes L, Sayles PC, Duso DK, Eaton SM, Lepak NM et al (2000) Reciprocal regulation of polarized cytokine production by effector B and T cells. Nat Immunol 1:475–482

    Article  CAS  PubMed  Google Scholar 

  • High KP (2005) Chronic infection and frailty: surrogate markers, associations, and causality. J Am Geriatr Soc 53:906–908

    Article  PubMed  Google Scholar 

  • Jylhä M, Paavilainen P, Lehtimäki T, Goebeler S, Karhunen PJ, Hervonen A et al (2007) Interleukin-1 receptor antagonist, interleukin-6, and C-reactive protein as predictors of mortality in nonagenarians: the vitality 90+ study. J Gerontol A Biol Sci Med Sci 62:1016–1021

    PubMed  Google Scholar 

  • Kong KF, Delroux K, Wang X, Qian F, Arjona A, Malawista SE et al (2008) Dysregulation of TLR3 impairs the innate immune response to West Nile virus in the elderly. J Virol 82:7613–7623

    Article  CAS  PubMed  Google Scholar 

  • Licastro F, Candore G, Lio D, Porcellini E, Colonna-Romano G, Franceschi C et al (2005) Innate immunity and inflammation in ageing: a key for understanding age related diseases. Immun Ageing 2:8

    Article  PubMed  Google Scholar 

  • Listì F, Candore G, Modica MA, Russo M, Di Lorenzo G, Esposito-Pellitteri M et al (2006) A study of serum immunoglobulin levels in elderly persons that provides new insights into B cell immunosenescence. Ann N Y Acad Sci 1089:487–495

    Article  PubMed  Google Scholar 

  • Listì F, Caruso M, Incalcaterra E, Hoffmann E, Caimi G, Balistreri CR et al (2008) Pro-inflammatory gene variants in myocardial infarction and longevity: implications for pharmacogenomics. Curr Pharm Des 14:2678–2685

    Article  PubMed  Google Scholar 

  • Martin F, Chan AC (2006) B cell immunobiology in disease: evolving concepts from the clinic. Annu Rev Immunol 24:467–496

    Article  CAS  PubMed  Google Scholar 

  • Miyaji C, Watanabe H, Toma H, Akisaka M, Tomiyama K, Sato Y et al (2000) Functional alteration of granulocytes, NK cells, and natural killer T cells in centenarians. Hum Immunol 61:908–916

    Article  CAS  PubMed  Google Scholar 

  • Niwa Y, Kasama T, Miyachi Y, Kanoh T (1989) Neutrophil chemotaxis, phagocytosis and parameters of reactive oxygen species in human aging: cross-sectional and longitudinal studies. Life Sci 44:1655–1664

    Article  CAS  PubMed  Google Scholar 

  • Oeppen J, Vaupel JW (2002) Demography. Broken limits to life expectancy. Science 296:1029–1031

    Article  CAS  PubMed  Google Scholar 

  • Ogata K, An E, Shioi Y, Nakamura K, Luo S, Yokose N et al (2001) Association between natural killer cell activity and infection in immunologically normal elderly people. Clin Exp Immunol 124:392–397

    Article  CAS  PubMed  Google Scholar 

  • Olshansky SJ, Ault AB (1986) The fourth stage of the epidemiologic transition: the age of delayed degenerative diseases. Milbank Q 64:355–391

    Article  CAS  PubMed  Google Scholar 

  • Ostan R, Bucci L, Capri M, Salvioli S, Scurti M, Pini E et al (2008) Immunosenescence and immunogenetics of human longevity. Neuroimmunomodulation 15:224–240

    Article  CAS  PubMed  Google Scholar 

  • Panda A, Arjona A, Sapey E, Bai F, Fikrig E, Montgomery RR et al (2009) Human innate immunosenescence: causes and consequences for immunity in old age. Trends Immunol 30:325–333

    Article  CAS  PubMed  Google Scholar 

  • Pawelec G, Akbar A, Caruso C, Effros R, Grubeck-Loebenstein B, Wikby A (2004) Is immunosenescence infectious? Trends Immunol 25:406–410

    Article  CAS  PubMed  Google Scholar 

  • Pawelec G, Akbar A, Caruso C, Solana R, Grubeck-Loebenstein B, Wikby A (2005) Human immunosenescence: is it infectious? Immunol Rev 205:257–268

    Article  CAS  PubMed  Google Scholar 

  • Pawelec G, Derhovanessian E, Larbi A, Strindhall J, Wikby A (2009) Cytomegalovirus and human immunosenescence. Rev Med Virol 19:47–56

    Article  CAS  PubMed  Google Scholar 

  • Rattan SI (2008) Hormesis in aging. Ageing Res Rev 7:63–78

    Article  PubMed  Google Scholar 

  • Rea IM, Candore G, Cavallone L, Olivieri F, Cardelli M, Franceschi C et al (2006) Longevity. In: Vandenbroeck K (ed) Cytokine gene polymorphisms in multifactorial conditions. CRC Press, Boca Raton, pp 379–394

  • Salvioli S, Olivieri F, Marchegiani F, Cardelli M, Santoro A, Bellavista E et al (2006) Genes, ageing and longevity in humans: problems, advantages and perspectives. Free Radic Res 40:1303–1323

    Article  CAS  PubMed  Google Scholar 

  • Sansoni P, Vescovini R, Fagnoni F, Biasini C, Zanni F, Zanlari L et al (2008) The immune system in extreme longevity. Exp Gerontol 63:61–65

    Article  Google Scholar 

  • Sanz I, Wei C, Lee FE, Anolik J (2008) Phenotypic and functional heterogeneity of human memory B cells. Semin Immunol 20:67–82

    Article  CAS  PubMed  Google Scholar 

  • Shi Y, Agematsu K, Ochs HD, Sugane K (2003) Functional analysis of human memory B-cell subpopulations: IgD+CD27+ B cells are crucial in secondary immune response by producing high affinity IgM. Clin Immunol 108:128–137

    Article  CAS  PubMed  Google Scholar 

  • Shi Y, Yamazaki T, Okubo Y, Uehara Y, Sugane K, Agematsu K (2005) Regulation of aged humoral immune defense against pneumococcal bacteria by IgM memory B cell. J Immunol 175:3262–3267

    CAS  PubMed  Google Scholar 

  • Szabo P, Li F, Mathew J, Lillvis J, Weksler ME (2004) Evolution of B-cell clonal expansions with age. Cell Immunol 231:158–167

    Article  CAS  PubMed  Google Scholar 

  • Troen BR (2003) The biology of aging. Mt Sinai J Med 70:3–22

    PubMed  Google Scholar 

  • Trzonkowski P, Myśliwska J, Szmit E, Wieckiewicz J, Lukaszuk K, Brydak LB et al (2003) Association between cytomegalovirus infection, enhanced proinflammatory response and low level of anti-hemagglutinins during the anti-influenza vaccination-an impact of immunosenescence. Vaccine 21:3826–3836

    Article  CAS  PubMed  Google Scholar 

  • van Duin D, Allore HG, Mohanty S, Ginter S, Newman FK et al (2007) Prevaccine determination of the expression of costimulatory B7 molecules in activated monocytes predicts influenza vaccine responses in young and older adults. J Infect Dis 195:1590–1597

    Article  PubMed  Google Scholar 

  • Vasto S, Candore G, Balistreri CR, Caruso M, Colonna-Romano G, Grimaldi MP et al (2007) Inflammatory networks in ageing, age-related diseases and longevity. Mech Ageing Dev 128:83–91

    Article  CAS  PubMed  Google Scholar 

  • Vasto S, Candore G, Listì F, Balistreri CR, Colonna-Romano G, Malavolta M et al (2008) Inflammation, genes and zinc in Alzheimer’s disease. Brain Res Rev 58:96–105

    Article  CAS  PubMed  Google Scholar 

  • Vasto S, Carruba G, Lio D, Colonna-Romano G, Di Bona D, Candore G et al (2009) Inflammation, ageing and cancer. Mech Ageing Dev 130:40–45

    Article  CAS  PubMed  Google Scholar 

  • Vasto S, Scapagnini G, Bulati M, Candore G, Castiglia L, Colonna-Romano G et al (2010) Biomarkers of ageing. Front Biosci 2:392–402

    Article  Google Scholar 

  • Vescovini R, Biasini C, Fagnoni FF, Telera AR, Zanlari L, Pedrazzoni M et al (2007) Massive load of functional effector CD4+ and CD8+ T cells against cytomegalovirus in very old subjects. J Immunol 179:4283–4291

    CAS  PubMed  Google Scholar 

  • Viveros MP, Arranz L, Hernanz A, Miquel J, De la Fuente M (2007) A model of premature aging in mice based on altered stress-related behavioral response and immunosenescence. Neuroimmunomodulation 14:157–162

    Article  CAS  PubMed  Google Scholar 

  • Wei C, Anolik J, Cappione A, Zheng B, Pugh-Bernard A, Brooks J et al (2007) A new population of cells lacking expression of CD27 represents a notable component of the B cell memory compartment in systemic lupus erythematosus. J Immunol 178:6624–6633

    CAS  PubMed  Google Scholar 

Download references

Acknowledgement

This work was supported by grants from Palermo University to GC, CC and GCR.

Author information

Authors and Affiliations

  1. Immunopathology Laboratory, Department of Pathobiology and Medical and Forensic Biotechnologies, University of Palermo, Corso Tukory 211, 90134, Palermo, Italy

    Giuseppina Candore, Calogero Caruso & Giuseppina Colonna-Romano

Authors
  1. Giuseppina Candore
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Calogero Caruso
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Giuseppina Colonna-Romano
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Calogero Caruso.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Candore, G., Caruso, C. & Colonna-Romano, G. Inflammation, genetic background and longevity. Biogerontology 11, 565–573 (2010). https://doi.org/10.1007/s10522-010-9286-3

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10522-010-9286-3

Keywords

Search

Navigation