The inflammation hypothesis of aging: molecular modulation by calorie restriction.

Current evidence strongly indicates that reactive oxygen species (ROS) and reactive nitrogen species (RNS) are widely implicated in the inflammatory process. However, mechanistic information is not readily available on the extent to which ROS/RNS contributes to the proinflammatory states of the aging process. The involvement of the underlying inflammation during the aging process and the molecular delineation of anti-inflammatory action of calorie restriction (CR) is described. Age-related upregulations of NF-kappaB, IL-beta, IL-6, TNFalpha, cyclooxygenase-2, and inducible NO synthase are all attenuated by CR. The suppression of the NF-kappaB activation was accomplished by blocking the dissociation of inhibitory IkappaBalpha and IkappaBbeta by CR. These findings provide underlying molecular insights into the anti-inflammatory action of CR in relation to the aging process. Based on these and other available data, it is suggested that the "Inflammation Hypothesis of Aging" supports the molecular basis of the inflammatory process as a plausible cause of the aging process.