Molecular mechanisms of aging-associated inflammation.
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.
Department of Pathology, Herbert Irving Comprehensive Cancer Center, College of Physicians & Surgeons, Columbia University Medical Center, New York, NY 10032, USA.
Devanand
D
Sarkar
Paul B
PB
Fisher
D000111:Acetylcysteine / Q000494:pharmacology; D000375:Aging / Q000378:metabolism*; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology; D045744:Cell Line, Tumor; D016922:Cellular Senescence; D018925:Chemokines / Q000378:metabolism; D016207:Cytokines / Q000378:metabolism; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005095:Exoribonucleases / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D005609:Free Radicals / Q000737:chemistry / Q000378:metabolism; D006801:Humans; D007249:Inflammation / Q000188:drug therapy / Q000209:etiology / Q000378:metabolism*; D016328:NF-kappa B / Q000235:genetics / Q000378:metabolism; D019636:Neurodegenerative Diseases / Q000188:drug therapy / Q000209:etiology / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism; D024101:Mitochondrial Proteins
D000111:Acetylcysteine; D000893:Anti-Inflammatory Agents; D018925:Chemokines; D016207:Cytokines; D004791:Enzyme Inhibitors; D005095:Exoribonucleases; D005609:Free Radicals; D016328:NF-kappa B; D017382:Reactive Oxygen Species; C476417:PNPT1 protein, human; D024101:Mitochondrial Proteins