A recent proposal of molecular inflammation hypothesis of the aging highlights this redox derangement as a plausible link between the normal aging process and age-related diseases. The hypothesis focused on the experimental observations revealing the dysregulated gene expression and transcription factors under the age-related oxidative stress. In this review, the biochemical and molecular bases of the inflammatory process will be delineated as the possible molecular mechanism for the aging and the age-related diseases. The key players involved in the proposed mechanism are the age-related upregulation of NF-κB and its regulated proinflammatory medators, all of which are attenuated by anti-aging calorie restriction (CR). Furthermore, data will be presented to describe molecular events leading to the age-related NF-κB activation, while CR blunted these activation processes. Based on these and other recent evidence, we propose to use molecular inflammation to emphasize the increased molecular proinflammatory reactions with aging, thus predisposing the aged organism to fully expressed chronic inflammatory phenomena. Restriction of calorie consumed extends longevity in many organisms. In rodents, CR showed reduction of plasma glucose and insulin-like growth factor (IGF-1) and postpones or attenuates cancer, immunosenescence, and inflammation. In organisms ranging yeast to mice, mutations in energy metabolism regulated genes (i.e. glucose or IGF-1 like signaling) extend life-span. Understandings of molecular inflammation hypothesis and life-expending energy metabolism including CR, should provide templates for anti-aging strategy and drugs that regulate aging process and age-related diseases. (Cancer Prev Res 10, 6-17, 2005)

Keywords: Molecular inflammation, Aging, Calorie restriction, Energy metabolism