Skip to main content
SpringerLink
Log in

Inflammaging and Its Role in Ageing and Age-Related Diseases

  • Chapter
  • First Online:
Evolutionary Thinking in Medicine

Abstract

Population ageing and the increase in age-related diseases are important issues for medicine and public health. A low-grade chronic pro-inflammatory status and a continuous/persistent antigenic load are a major characteristic of the ageing process called inflammaging and represent a mechanism at the basis of most age-related disorders. Thus, inflammation is a relevant target for treatment and medical intervention. In this chapter, we posit inflammaging within an evolutionary perspective to elucidate its biological complexity, i.e. the common evolutionary basis of stress response, inflammation and innate immunity, and to better understand population dynamics and individual lifelong trajectories. We will start with a brief description of human immunosenescence, antagonistic pleiotropy and the two-hits theory, as a background of the concept of healthy ageing. Then, the link between inflammaging and environment is illustrated by introducing the concept of immunological biography, in order to contextualize inflammaging within a lifelong human eco-anthropological perspective. This comprehensive approach includes the socio-cultural determinants as an essential component that plays a substantial role in triggering and maintaining the age-related inflammatory processes. In conclusion, the evolutionary perspective offers a unifying conceptual framework to better identify strategies able to decrease the rate of inflammaging starting from early life and with beneficial effects in old people. Dietary interventions are proposed as an example of an integrative approach capable of modulating inflammation and reducing the genetic risk of pathologies.

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 89.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 119.99
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

Abbreviations

IS:

Immune system

NES:

Neuro-endocrine system

POMC:

Pro-opiomelanocortin

BA:

Biogenic amines

NOS:

Nitric oxide synthase

ACTH:

Adrenocorticotrophic hormone

CRH:

Corticotrophin-releasing hormone

References

  1. Cartledge B (1998) Mind, brain, and the environment. Oxford University Press, Oxford/New York

    Google Scholar 

  2. Franceschi C, Bonafè M, Valensin S et al (2000) Inflamm-aging. An evolutionary perspective on immunosenescence. Ann NY Acad Sci 908:244–254

    Article  CAS  PubMed  Google Scholar 

  3. Morrisette-Thomas V, Cohen AA, Fülöp T et al (2014) Inflamm-aging does not simply reflect increases in pro-inflammatory markers. Mech Ageing Dev 139:49–57. doi:10.1016/j.mad.2014.06.005

    Article  CAS  PubMed  Google Scholar 

  4. Franceschi C, Campisi J (2014) Chronic inflammation (inflammaging) and its potential contribution to age-associated diseases. J Gerontol A Biol Sci Med Sci 69:S4–S9. doi:10.1093/gerona/glu057

    Article  PubMed  Google Scholar 

  5. Okin D, Medzhitov R (2012) Evolution of inflammatory diseases. Curr Biol CB 22:R733–R740. doi:10.1016/j.cub.2012.07.029

    Article  CAS  PubMed  Google Scholar 

  6. Ottaviani E, Franceschi C (1996) The neuroimmunology of stress from invertebrates to man. Prog Neurobiol 48:421–440

    Article  CAS  PubMed  Google Scholar 

  7. Blalock JE (1989) A molecular basis for bidirectional communication between the immune and neuroendocrine systems. Physiol Rev 69:1–32

    CAS  PubMed  Google Scholar 

  8. Ottaviani E, Malagoli D, Franceschi C (2007) Common evolutionary origin of the immune and neuroendocrine systems: from morphological and functional evidence to in silico approaches. Trends Immunol 28:497–502. doi:10.1016/j.it.2007.08.007

    Article  CAS  PubMed  Google Scholar 

  9. Holzer P, Farzi A (2014) Neuropeptides and the microbiota-gut-brain axis. Adv Exp Med Biol 817:195–219. doi:10.1007/978-1-4939-0897-4_9

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  10. Kitano H (2007) Towards a theory of biological robustness. Mol Syst Biol 3:137. doi:10.1038/msb4100179

    Article  PubMed  PubMed Central  Google Scholar 

  11. Csete M, Doyle J (2004) Bow ties, metabolism and disease. Trends Biotechnol 22:446–450. doi:10.1016/j.tibtech.2004.07.007

    Article  CAS  PubMed  Google Scholar 

  12. Ottaviani E, Malagoli D, Capri M, Franceschi C (2008) Ecoimmunology: is there any room for the neuroendocrine system? BioEssays 30:868–874. doi:10.1002/bies.20801

    Article  PubMed  Google Scholar 

  13. Franceschi C, Bonafè 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 

  14. Franceschi C, Monti D, Barbieri D et al (1995) Immunosenescence in humans: deterioration or remodelling? Int Rev Immunol 12:57–74. doi:10.3109/08830189509056702

    Article  CAS  PubMed  Google Scholar 

  15. Franceschi C, Valensin S, Bonafè M et al (2000) The network and the remodeling theories of aging: historical background and new perspectives. Exp Gerontol 35:879–896

    Article  CAS  PubMed  Google Scholar 

  16. Franceschi C, Capri M, Monti D et al (2007) Inflammaging and anti-inflammaging: a systemic perspective on aging and longevity emerged from studies in humans. Mech Ageing Dev 128:92–105. doi:10.1016/j.mad.2006.11.016

    Article  CAS  PubMed  Google Scholar 

  17. Gems D, Partridge L (2008) Stress-response hormesis and aging: “that which does not kill us makes us stronger”. Cell Metab 7:200–203. doi:10.1016/j.cmet.2008.01.001

    Article  CAS  PubMed  Google Scholar 

  18. Ingold T (2000) The perception of the environment: essays on livelihood, dwelling and skill. Routledge, London/New York

    Book  Google Scholar 

  19. Raj T, Kuchroo M, Replogle JM et al (2013) Common risk alleles for inflammatory diseases are targets of recent positive selection. Am J Hum Genet 92:517–529. doi:10.1016/j.ajhg.2013.03.001

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  20. Rose M, Charlesworth B (1980) A test of evolutionary theories of senescence. Nature 287:141–142

    Article  CAS  PubMed  Google Scholar 

  21. Hughes KA, Alipaz JA, Drnevich JM, Reynolds RM (2002) A test of evolutionary theories of aging. Proc Natl Acad Sci USA 99:14286–14291. doi:10.1073/pnas.222326199

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  22. Parsons PA (2007) Antagonistic pleiotropy and the stress theory of aging. Biogerontology 8:613–617. doi:10.1007/s10522-007-9101-y

    Article  PubMed  Google Scholar 

  23. Capri M, Salvioli S, Monti D et al (2008) Human longevity within an evolutionary perspective: the peculiar paradigm of a post-reproductive genetics. Exp Gerontol 43:53–60. doi:10.1016/j.exger.2007.06.004

    Article  PubMed  Google Scholar 

  24. Grignolio A, Mishto M, Faria AMC et al (2014) Towards a liquid self: how time, geography, and life experiences reshape the biological identity. Front Immunol 5:153. doi:10.3389/fimmu.2014.00153

    Article  PubMed  PubMed Central  Google Scholar 

  25. Ulijaszek SJ (1995) Human energetics in biological anthropology. Cambridge University Press, Cambridge/New York

    Google Scholar 

  26. Ulijaszek SJ, Mann N, Elton S (2012) Evolving human nutrition: implications for public health. Cambridge University Press, New York

    Book  Google Scholar 

  27. Trevathan W, Smith EO, McKenna JJ (2008) Evolutionary medicine and health: new perspectives. Oxford University Press, New York

    Google Scholar 

  28. Banwell C, Ulijaszek S, Dixon J (2013) When culture impacts health—global lessons for effective health research. Elsevier, Amsterdam

    Google Scholar 

  29. Moretti E, Castro I, Franceschi C, Basso B (2010) Chagas disease: serological and electrocardiographic studies in Wichì and Creole communities of Misión Nueva Pompeya, Chaco, Argentina. Mem Inst Oswaldo Cruz 105:621–627

    Google Scholar 

  30. Sevini F, Yao DY, Lomartire L et al (2013) Analysis of population substructure in two sympatric populations of Gran Chaco. PLoS ONE, Argentina. doi:10.1371/journal.pone.0064054

    Google Scholar 

  31. Franceschi ZA, Dasso MC (2010) Etno-grafías: la escritura como testimonio entre los wichí. Corregidor, Buenos Aires

    Google Scholar 

  32. Morello JH, Rodriguez AF (2009) El Chaco sin bosques: La Pampa o el desierto del futuro, 1a ed. Orientación Gráfica Editora, Buenos Aires

    Google Scholar 

  33. Torres GF, Santoni ME, Romero LN (2007) Los Wichi del Chaco Salteño: ayer y hoy: alimentación y nutrición. Crisol, Salta

    Google Scholar 

  34. Franceschi ZA, Peveri V (2014) Raccontare di gusto - Arti del cibo e della memoria in America latina e Africa, ETS

    Google Scholar 

  35. Burger O, Baudisch A, Vaupel JW (2012) Human mortality improvement in evolutionary context. Proc Natl Acad Sci USA 109:18210–18214. doi:10.1073/pnas.1215627109

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  36. Corella D, Carrasco P, Sorlí JV et al (2013) Mediterranean diet reduces the adverse effect of the TCF7L2-rs7903146 polymorphism on cardiovascular risk factors and stroke incidence: a randomized controlled trial in a high-cardiovascular-risk population. Diab Care 36:3803–3811. doi:10.2337/dc13-0955

    Article  CAS  Google Scholar 

  37. Jenkins DA, Kendall CC, Marchie A et al (2003) EFfects of a dietary portfolio of cholesterol-lowering foods vs lovastatin on serum lipids and c-reactive protein. JAMA 290:502–510. doi:10.1001/jama.290.4.502

    Article  CAS  PubMed  Google Scholar 

  38. Ros E (2009) Nuts and novel biomarkers of cardiovascular disease. Am J Clin Nutr 89:1649S–1656S. doi:10.3945/ajcn.2009.26736R

    Article  CAS  PubMed  Google Scholar 

  39. Kendall CWC, Josse AR, Esfahani A, Jenkins DJA (2010) Nuts, metabolic syndrome and diabetes. Br J Nutr 104:465–473. doi:10.1017/S0007114510001546

    Article  CAS  PubMed  Google Scholar 

  40. Wannamethee SG, Whincup PH, Thomas MC, Sattar N (2009) Associations between dietary fiber and inflammation, hepatic function, and risk of type 2 diabetes in older men: potential mechanisms for the benefits of fiber on diabetes risk. Diab Care 32:1823–1825. doi:10.2337/dc09-0477

    Article  CAS  Google Scholar 

  41. Ghanim H, Chaudhuri A, Dandona P et al (2010) Associations between dietary fiber and inflammation, hepatic function, and risk of type 2 Diabetes in older men: potential mechanisms for the benefits of fiber on diabetes risk response to Wannamethee et al. Diab Care 33:e43–e43. doi:10.2337/dc09-2127

    Article  Google Scholar 

  42. Salvioli S, Sikora E, Cooper EL, Franceschi C (2007) Curcumin in cell death processes: a challenge for CAM of age-related pathologies. Evid-Based Complement Altern Med ECAM 4:181–190. doi:10.1093/ecam/nem043

    Article  CAS  Google Scholar 

  43. Biagi E, Nylund L, Candela M et al (2010) Through ageing, and beyond: gut microbiota and inflammatory status in seniors and centenarians. PLoS ONE 5:e10667. doi:10.1371/journal.pone.0010667

    Article  PubMed  PubMed Central  Google Scholar 

  44. Collino S, Montoliu I, Martin F-PJ et al (2013) Metabolic signatures of extreme longevity in northern Italian centenarians reveal a complex remodeling of lipids, amino acids, and gut microbiota metabolism. PLoS ONE 8:e56564. doi:10.1371/journal.pone.0056564

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  45. Quercia S, Candela M, Giuliani C et al (2014) From lifetime to evolution: timescales of human gut microbiota adaptation. Front Microbiol 5:587. doi:10.3389/fmicb.2014.00587

    Article  PubMed  PubMed Central  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Experimental, Diagnostic and Specialty Medicine (DIMES), University of Bologna, Bologna, Italy

    Prof. Claudio Franceschi Ph.D. & Paolo Garagnani Ph.D.

  2. Interdepartmental Center “Luigi Galvani” (CIG), University of Bologna, Bologna, Italy

    Prof. Claudio Franceschi Ph.D. & Paolo Garagnani Ph.D.

  3. IRCCS Institute of Neurological Sciences, and CNR-ISOF, Bologna, Italy

    Prof. Claudio Franceschi Ph.D.

  4. Department of History, Cultures and Civilizations (DISCI), University of Bologna, Bologna, Italy

    Zelda Alice Franceschi Ph.D.

  5. Department of Biological, Geological and Environmental Sciences (BiGeA), Laboratory of Molecular Anthropology and Centre for Genome Biology, University of Bologna, Bologna, Italy

    Cristina Giuliani Ph.D.

Authors
  1. Prof. Claudio Franceschi Ph.D.
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Zelda Alice Franceschi Ph.D.
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Paolo Garagnani Ph.D.
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Cristina Giuliani Ph.D.
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Claudio Franceschi Ph.D. .

Editor information

Editors and Affiliations

  1. Oxford, United Kingdom

    Alexandra Alvergne

  2. Oxford, United Kingdom

    Crispin Jenkinson

  3. Paris, France

    Charlotte Faurie

Glossary

Antagonistic pleiotropy theory of ageing

This hypothesis was first proposed by Williams in 1957 who suggested that a certain gene variant can be beneficial in early life (fitness), while it can become detrimental later in life

Biodemographic dynamics

The analysis of demography within an evolutionary biology context, with particular attention on events that impact on human population structure, such as colonization, migrations and expansion

Ecoimmunology

Discipline that integrates the analysis of the immune system function within animal biology and that considers the interaction between an organism and their ecological environment during evolution

Garbaging

The exogenous and endogenous inflammatory stimuli that, as a whole, increase progressively with age and trigger inflammaging

Heterochronic parabiosis

Parabiosis is an experimental model where two animals, here mice, are joined together surgically to create shared blood circulation. Heterochronic parabiosis indicates that the two animals joined together are of different ages (one old and one young)

Hormesis

Literally from Greek it means “to stimulate”, and it indicates the ability of respond positively to low amounts of substances (or stressors) that would otherwise be highly toxic at higher concentrations

IL-6

Interleukin 6 (IL-6) is a cytokine with various biological functions, among which a role in the acute phase response. It is secreted by T cells and macrophages to stimulate the immune response and acts as both a pro-inflammatory and an anti-inflammatory cytokine. It is also a myokine discharged into the bloodstream after muscle contraction and acts to increase the breakdown of fats and to improve insulin resistance

Immunological space

is a metaphor to conceptualize the IS as a whole from a spatial (volume) point of view. During immunosenescence, a progressive accumulation of clones of memory cells tends to fill the “immunological space”, reducing the number of other immune cells, such as naïve T cells, and the possibility to respond to new antigens

Inflammaging

Human ageing is characterized by a chronic, low-grade inflammation (high levels of inflammatory cytokines and other inflammatory markers such as C-reactive protein), and this phenomenon has been termed “inflammaging”. Inflammaging is a highly significant risk factor for both morbidity and mortality in the elderly, as the vast majority of age-related diseases share an inflammatory pathogenesis

Rights and permissions

Reprints and permissions

Copyright information

© 2016 Springer International Publishing Switzerland

About this chapter

Cite this chapter

Franceschi, C., Franceschi, Z.A., Garagnani, P., Giuliani, C. (2016). Inflammaging and Its Role in Ageing and Age-Related Diseases. In: Alvergne, A., Jenkinson, C., Faurie, C. (eds) Evolutionary Thinking in Medicine. Advances in the Evolutionary Analysis of Human Behaviour. Springer, Cham. https://doi.org/10.1007/978-3-319-29716-3_18

Download citation

  • DOI: https://doi.org/10.1007/978-3-319-29716-3_18

  • Published:

  • Publisher Name: Springer, Cham

  • Print ISBN: 978-3-319-29714-9

  • Online ISBN: 978-3-319-29716-3

  • eBook Packages: MedicineMedicine (R0)

Publish with us

Policies and ethics

Search

Navigation