Werner Syndrome as an example of inflamm-aging: possible therapeutic opportunities for a progeroid syndrome?
Werner syndrome (WS) is a premature aging disorder that is widely used as a model for some aspects of the normal human aging process. Individuals with WS have several of the characteristics of normal aging, such as cataracts, hair graying, and skin aging, but manifest these at an early age. In addition, WS is associated with high levels of inflammatory diseases such as atherosclerosis and type II diabetes. Recent data have indicated that fibroblasts derived from individuals with WS have activated a major molecular pathway involved in inflammation. This observation ties in with the presence of high plasma levels of inflammatory cytokines in individuals with WS. In this paper, the authors discuss the possibility that WS is an example of "inflamm-aging," in that many of the phenotypic manifestations may result from an increased inflammatory state. Moreover, drugs that specifically block this inflammation pathway may be possible candidates for therapeutic intervention in WS.
Davis
Terence
T
Department of Pathology, Cardiff University School of Medicine, Wales, United Kingdom. davist2@cardiff.ac.uk
Kipling
David
D
D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000627:therapeutic use; D016922:Cellular Senescence / Q000502:physiology; D004265:DNA Helicases / Q000378:metabolism; D005090:Exodeoxyribonucleases; D005347:Fibroblasts / Q000502:physiology; D006801:Humans; D007093:Imidazoles / Q000627:therapeutic use; D007249:Inflammation / Q000473:pathology*; D018799:Intercellular Adhesion Molecule-1 / Q000378:metabolism; D009154:Mutation; D011725:Pyridines / Q000627:therapeutic use; D053484:RecQ Helicases; D015398:Signal Transduction; D014898:Werner Syndrome / Q000188:drug therapy / Q000235:genetics / Q000473:pathology* / Q000503:physiopathology; D000071657:Werner Syndrome Helicase; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism
D000894:Anti-Inflammatory Agents, Non-Steroidal; D007093:Imidazoles; D011725:Pyridines; D018799:Intercellular Adhesion Molecule-1; D048051:p38 Mitogen-Activated Protein Kinases; D005090:Exodeoxyribonucleases; D004265:DNA Helicases; D053484:RecQ Helicases; C098785:WRN protein, human; D000071657:Werner Syndrome Helicase; C093642:SB 203580