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Cytokine Expression and Production Changes in Very Old Age

  • Living reference work entry
  • First Online:
Handbook of Immunosenescence

Abstract

The immune system is a dynamic whole system network that, as a result of the interaction between genes, lifestyle and environment, is constantly remodeling itself throughout our lifespan. The immune response is driven by the complex interactions of up- and downregulating cytokines and chemokines. These families of proteins fine-tune effective responses to infection or tissue damage, through multiple layers of activation and control, regulated by soluble receptors, receptor antagonists, and diverse serum mediators, in order to maintain homeostatic immune balance.

With age, the immune system shows a persistent low-grade inflammation, controlled by the balance between pro-inflammatory and anti-inflammatory cytokines. A loosening of this cytokine balance has been called “inflamm-aging” or sterile inflammation and underpins most age-related disease from atherosclerosis, to diabetes, to Alzheimer’s disease, and aging itself. “Inflamm-aging” may derive in part, from age-related increases in senescence-associated secretory phenotype cells, which secrete pro-inflammatory mediators, together with an age-related decline in homeostatic immune function, increased fragility of epithelial barriers, and changes in the gut microbiome. Cytokine expression is known to be influenced by the local cellular environment, which accumulates age-related damage from reactive oxygen species, DNA and lipid damage, or incorrectly folded proteins.

Increasing knowledge about the molecular pathways underpinning the pro-inflammatory cytokine network should allow the development of therapeutic tools to reduce senescence-associated secretory phenotype cells or the use of deacetylating and demethylation agents to modify gene expression. At the human level, emerging understanding of the importance of external environments and the epigenome suggests that behavioral changes in lifestyle through diet, exercise, or social networks can and do influence the immune system.

Susan E. McNerlan and I. Maeve Rea contributed equally to this work.

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    Authors and Affiliations

    1. Regional Cytogenetics Laboratory, Belfast Health and Social Care Trust, Belfast, Northern Ireland, UK

      Susan E. McNerlan

    2. Department of Neuroscience, Mayo Clinic College of Medicine, Mayo Clinic Graduate School of Biomedical Sciences, Jacksonville, FL, USA

      Owen A. Ross

    3. Department of Clinical Genomics, Mayo Clinic College of Medicine, Jacksonville, FL, USA

      Owen A. Ross

    4. Department of Biology, University of North Florida, Jacksonville, FL, USA

      Owen A. Ross

    5. School of Medicine and Medical Science, University College Dublin, Dublin, Ireland

      Owen A. Ross

    6. Mayo Graduate School, Neurobiology of Disease Track, Mayo Clinic, Jacksonville, FL, USA

      Owen A. Ross

    7. School of Medicine, Dentistry and Biomedical Science, Queens University Belfast, Belfast, Northern Ireland, UK

      I. Maeve Rea

    8. Northern Ireland Centre for Stratified Medicine, C-TRIC, Altnagelvin Hospital, Ulster University, Londonderry, Northern Ireland, UK

      I. Maeve Rea

    9. Care of Elderly Medicine, Belfast Health and Social Care Trust, Belfast, Northern Ireland, UK

      I. Maeve Rea

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    1. Susan E. McNerlan
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    3. I. Maeve Rea
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    Correspondence to I. Maeve Rea .

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    Editors and Affiliations

    1. Division of Geriatrics Research Center on Aging, University of Sherbrooke Dept. of Medicine, Sherbrooke, Québec, Canada

      Tamas Fulop

    2. Dept of Experimental Pathology, University of Bologna, Bologna, Italy

      Claudio Franceschi

    3. Institute for Health and Life Sciences, Tokyo, Japan

      Katsuiku Hirokawa

    4. Center for Medical Research, University of Tübingen, Tübingen, Germany

      Graham Pawelec

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    1. Research Center on Aging, Department of Medicine, Immunology Graduate Programme, Faculty of Medicine, University of Sherbrooke, Sherbrooke, Quebec, Canada

      Tamas Fulop

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    McNerlan, S.E., Ross, O.A., Maeve Rea, I. (2018). Cytokine Expression and Production Changes in Very Old Age. In: Fulop, T., Franceschi, C., Hirokawa, K., Pawelec, G. (eds) Handbook of Immunosenescence. Springer, Cham. https://doi.org/10.1007/978-3-319-64597-1_40-1

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