Molecular inflammation as an underlying mechanism of the aging process and age-related diseases

J Dent Res. 2011 Jul;90(7):830-40. doi: 10.1177/0022034510387794. Epub 2011 Mar 29.


Aging is a biological process characterized by time-dependent functional declines that are influenced by changes in redox status and by oxidative stress-induced inflammatory reactions. An organism's pro-inflammatory status may underlie the aging process and age-related diseases. In this review, we explore the molecular basis of low-grade, unresolved, subclinical inflammation as a major risk factor for exacerbating the aging process and age-related diseases. We focus on the redox-sensitive transcription factors, NF-κB and FOXO, which play essential roles in the expression of pro-inflammatory mediators and anti-oxidant enzymes, respectively. Major players in molecular inflammation are discussed with respect to the age-related up-regulation of pro-inflammatory cytokines and adhesion molecules, cyclo-oxygenase-2, lipoxygenase, and inducible nitric oxide synthase. The molecular inflammation hypothesis proposed by our laboratory is briefly described to give further molecular insights into the intricate interplay among redox balance, pro-inflammatory gene activation, and chronic age-related inflammatory diseases. The final section discusses calorie restriction as an aging-retarding intervention that also exhibits extraordinarily effective anti-inflammatory activity by modulating GSH redox, NF-κB, SIRT1, PPARs, and FOXOs.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Aging / physiology*
  • Animals
  • Atherosclerosis / metabolism
  • Caloric Restriction*
  • Cell Adhesion Molecules / metabolism
  • Chronic Periodontitis / metabolism
  • Forkhead Transcription Factors / metabolism
  • Humans
  • Inflammation / metabolism*
  • Inflammation Mediators / metabolism*
  • Lipoxygenase / metabolism
  • Metabolic Syndrome / metabolism
  • NF-kappa B / metabolism
  • Nitric Oxide Synthase Type II / metabolism
  • Osteoporosis / metabolism
  • Oxidative Stress / physiology*
  • Prostaglandin-Endoperoxide Synthases / metabolism
  • Signal Transduction


  • Cell Adhesion Molecules
  • Forkhead Transcription Factors
  • Inflammation Mediators
  • NF-kappa B
  • Lipoxygenase
  • Nitric Oxide Synthase Type II
  • Prostaglandin-Endoperoxide Synthases