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.