NLRP3 inflammasome activation in inflammaging

Semin Immunol. 2018 Dec:40:61-73. doi: 10.1016/j.smim.2018.09.001. Epub 2018 Sep 26.

Abstract

The process of aging is associated with the appearance of low-grade subclinical inflammation, termed inflammaging, that can accelerate age-related diseases. In Western societies the age-related inflammatory response can additionally be aggravated by an inflammatory response related to modern lifestyles and excess calorie consumption, a pathophysiologic inflammatory response that was coined metaflammation. Here, we summarize the current knowledge of mechanisms that drive both of these processes and focus our discussion the emerging concept that a key innate immune pathway, the NLRP3 inflammasome, is centrally involved in the recognition of triggers that appear during physiological aging and during metabolic stress. We further discuss how these processes are involved in the pathogenesis of common age-related pathologies and highlight potential strategies by which the detrimental inflammatory responses could be pharmacologically addressed.

Keywords: Aging; Inflammaging; Metaflammation; NLRP3 inflammasome; Proinflammatory cytokines.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Aging*
  • Animals
  • Cytokines / metabolism
  • Humans
  • Immunity, Innate
  • Inflammasomes / immunology*
  • Inflammation Mediators / metabolism
  • Inflammation*
  • Life Style
  • NLR Family, Pyrin Domain-Containing 3 Protein / metabolism*
  • Signal Transduction
  • Stress, Physiological / immunology*

Substances

  • Cytokines
  • Inflammasomes
  • Inflammation Mediators
  • NLR Family, Pyrin Domain-Containing 3 Protein