Molecular mechanisms of aging-associated inflammation.
Cancer Lett
; 236(1): 13-23, 2006 May 08.
Article
en En
| MEDLINE
| ID: mdl-15978720
ABSTRACT
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.
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Colección:
01-internacional
Asunto principal:
Envejecimiento
/
Exorribonucleasas
/
Inflamación
Tipo de estudio:
Etiology_studies
/
Risk_factors_studies
Límite:
Animals
/
Humans
Idioma:
En
Revista:
Cancer Lett
Año:
2006
Tipo del documento:
Article
País de afiliación:
Estados Unidos