Molecular mechanisms of aging-associated inflammation

Cancer Lett. 2006 May 8;236(1):13-23. doi: 10.1016/j.canlet.2005.04.009. Epub 2005 Jun 22.


A direct relationship exists between aging and increasing incidences of chronic diseases. In fact, with most age-associated diseases individuals manifest an underlying chronic inflammatory state as evidenced by local infiltration of inflammatory cells, such as macrophages, and higher circulatory levels of pro-inflammatory cytokines, complement components and adhesion molecules. Consequently, treatment with anti-inflammatory agents provide symptomatic relief to several aging-associated diseases, even as remote as Alzheimer's or Parkinson's disease, indicating that chronic inflammation may play a substantial role in the pathogenesis of these disease states. The molecular mechanisms underlying this chronic inflammatory condition during cellular senescence is presently unclear. Cellular damage by oxygen free radicals is a primary driving force for aging and increased activation of redox-regulated transcription factors, such as NF-kappaB that regulate the expression of pro-inflammatory molecules, has been documented in aged animals/individuals versus their young counterparts. Human polynucleotide phosphorylase (hPNPase(old-35)), a RNA degradation enzyme shown to be upregulated during differentiation and cellular senescence, may represent a molecular link between aging and its associated inflammation. hPNPase(old-35) promotes reactive oxygen species (ROS) production, activates the NF-kappaB pathway and initiates the production of pro-inflammatory cytokines, such as IL-6 and IL-8. In these contexts, inhibition of hPNPase(old-35) may represent a novel molecular target for intervening in aging-associated chronic diseases.

Publication types

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

MeSH terms

  • Acetylcysteine / pharmacology
  • Aging / metabolism*
  • Animals
  • Anti-Inflammatory Agents / pharmacology
  • Cell Line, Tumor
  • Cellular Senescence
  • Chemokines / metabolism
  • Cytokines / metabolism
  • Enzyme Inhibitors / pharmacology
  • Exoribonucleases / antagonists & inhibitors
  • Exoribonucleases / genetics
  • Exoribonucleases / metabolism*
  • Free Radicals / chemistry
  • Free Radicals / metabolism
  • Humans
  • Inflammation / drug therapy
  • Inflammation / etiology
  • Inflammation / metabolism*
  • NF-kappa B / genetics
  • NF-kappa B / metabolism
  • Neurodegenerative Diseases / drug therapy
  • Neurodegenerative Diseases / etiology
  • Neurodegenerative Diseases / metabolism
  • Reactive Oxygen Species / metabolism


  • Anti-Inflammatory Agents
  • Chemokines
  • Cytokines
  • Enzyme Inhibitors
  • Free Radicals
  • NF-kappa B
  • Reactive Oxygen Species
  • Exoribonucleases
  • PNPT1 protein, human
  • Acetylcysteine