The Molecular Inflammatory Process in Aging

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Abstract
Emerging pathological evidence indicates that major chronic aging-related diseases such as atherosclerosis, arthritis, dementia, osteoporosis, and cardiovascular diseases, are inflammation-related. In this review, inflammation is examined as a possible underlying basis for the molecular alterations that link aging and agerelated pathological processes. A proposal for the molecular inflammation hypothesis of the aging views the redox derangement that occurs during aging as the major factor for increased risk for age-related inflammation. Accumulated data strongly indicate the activation of redox-sensitive transcription factors and dysregulated gene expression under the age-related oxidative stress seems to be the major culprits. Key players involved in the inflammatory process are the age-related upregulation of NF-κB, IL-1β, IL-6, TNFα, cyclooxygenase-2, adhesion molecules, and inducible NO synthase. Furthermore, data are presented on the molecular events involved in age-related NF-κB activation and phosphorylation by IκB kinase/NIK and MAPKs. Experimental data on antiaging calorie restriction (CR) for its antiinflammatory efficacy by suppressing the upregulated proinflammatory mediators will be reviewed. Also, the involvement of another super family of transcription factors, PPARs (PPARα, γ) as regulators of proinflammatory responses and NF-κB signaling pathway is described as well as a discussion on the physiological significance of a well-maintained balance between NF-κB and PPARs.