[BME Colloquium] Molecular Inflammation as the Underlying Mechanism for the Aging and age-related diseases and Its Intervention
  • Hae Young Chung, Ph.D.(Pusan National University)
  • SLS Colloquia / Sep 11th, 2014 04:00 pm / EB1 E104
Experimental evidence consistently shows that increased oxidative stress causes a shift of the cellular redox balance toward to a high oxidative status in aged organisms. Subtle changes in the redox status is expected to cause serious consequences on the cellular metabolic activity because the cell’s survival depends on the proper coupling of reduction/oxidation reactions. A recent proposal of ‘molecular inflammation hypothesis of aging’ from our laboratory highlights this redox derangement as a causal link between inflammation and the normal aging process and age-related diseases. The hypothesis is based on the experimental observations on the activated pro-inflammatory gene expressions, transcription factors and altered signal pathways under the age-related oxidative stress. Research on life-extending calorie restriction (CR) provided the most consistent evidence that the suppression of inflammation may be the basis of its anti-aging action. For this presentation, data on the age-related up-regulation mechanism of NF-kappaB signaling, IL-1beta, IL-6, TNF-alpha, cyclooxygenase-2, and inducible NO synthase are discussed.  Also included in discussion are molecular and systems-biological evidence on age-related NF-kappaB activation with phosphorylation by IkappaB kinase/NIK and MAPKs. All of the above?mentioned events are blunted by CR, which served as the basis of proposed molecular inflammation hypothesis of aging. Recent CR works on the up-regulation of anti-inflammatory PPARs by CR and PPAR agonists cast further support the molecular inflammation hypothesis.  This inflammation hypothesis predicts  that  the aged organism with up-regulated chronic inflammatory status and  reduced anti-inflammatory PPARs activity  predipose  to chronic inflammatory diseases. This premise is in agreement with the current view that molecular inflammation is the major underlying risk factor for age-related diseases such as metabolic syndrome, cardiovascular disease, dementia, arthritis, diabetes, osteoporosis and cancers as occurring in the aged.