Age and Age-related Diseases: Role of Inflammation Triggers and Cytokines

Maeve. I. Rea, David S Gibson, Victoria E McGilligan, Susan E McNerlan, H. Denis Alexander, Owen A Ross

Research output: Contribution to journalArticle

149 Citations (Scopus)
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Abstract

Cytokine dysregulation is believed to play a key role in the remodeling of the immune system at older age, with evidence pointing to an inability to fine-control systemic inflammation, which seems to be a marker of unsuccessful aging. This reshaping of cytokine expression pattern, with a progressive tendency toward a pro-inflammatory phenotype has been called ‘inflamm-aging’. Despite much research there is no clear understanding about the causes of ‘inflamm-aging’ that underpin most major age-related diseases including atherosclerosis, diabetes, Alzheimer’s disease, rheumatoid arthritis, cancer and aging itself.Several common molecular pathways have been identified that are associated with both aging and low-grade inflammation. Excess oxidative stress and DNA damage triggers the inflammasome, stimulating NF‐κB and the IL‐1β‐mediated inflammatory cascade. Autophagy, the cell machinery process that removes damaged proteins and large aggregates, is slowed up at older age and in age-related disease, causing damaged material to accumulate and reduce cellular efficiency. Senescent cells increase with age and in age-related diseases and the associated senescence-associated secretory phenotype (SASP) that includes many pro-inflammatory cytokines and proteases, seems centrally involved in the pro-inflammatory milieu. The roles of bioactive resolvins and anti-inflammatory cytokines require clarification in the inflamm-aging phenomenon.The age-related change in redox balance, the increase in age-related senescent cells and SASP and the decline in effective autophagy that can trigger the inflammasome, suggest that it may be possible to delay age-related diseases and aging itself by suppressing pro-inflammatory molecular mechanisms or improving the timely resolution of inflammation. Conversely there may be learning from molecular or genetic pathways from long-lived cohorts who exemplify good quality aging. Here we will discuss some aspects of the present understanding of the molecular mechanisms that trigger inflammation and underpin the pro-inflammatory ageing-phenotype, which may lead to identification of useful therapeutic strategies and better quality ageing and longevity for all.
Original languageEnglish
JournalFrontiers in Immunology
Volume2018
Early online date9 Apr 2018
DOIs
Publication statusE-pub ahead of print - 9 Apr 2018

Keywords

  • Ageing
  • age-related diseases
  • Inflamm-aging
  • redox
  • Senescence SASP
  • Autophagy
  • Inflammasomes
  • Cytokine dysregulation
  • Inflammation resolution

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