Cytokine Expression and Production Changes in Very Old Age

Susan McNerlan, Owen Ross, Irene M Rea

Research output: Chapter in Book/Report/Conference proceedingChapter


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.
Original languageEnglish
Title of host publicationIn: Tamas Fulop, Claudio Franceschi, Katsuiku Hirokawa, Graham Pawelec (Eds.), Handbook of Immunosenescence, 1-24, 2018
Publication statusPublished - 01 Jan 2018


  • Immunosenescence; ageing

ASJC Scopus subject areas

  • Medicine(all)
  • Immunology and Microbiology(all)


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