Molecular inflammation hypothesis of aging based on the anti-aging mechanism of calorie restriction.
Accumulating evidence strongly suggests that oxidative stress underlies aging processes. Research provides consistent evidence that calorie restriction (CR) reduces age-related oxidative stress and has anti-inflammatory properties. However, information is lacking on the molecular mechanism that would better define the interrelation of reactive oxygen species and nitrogen species and the pro-inflammatory states of the aging process. In this review, the biochemical and molecular bases of the inflammatory process in the aging process are analyzed to delineate the molecular inflammation hypothesis of aging. The key players involved in the proposed hypothesis are the age-related upregulation of NF-kappa B, IL-1 beta, IL-6, TNFalpha, cyclooxygenase-2, and inducible NO synthase, all of which are attenuated by CR. Furthermore, age-related NF kappa B activation is associated with phosphorylation by I kappa B kinase/NIK and MAPKs, while CR blocked these activation processes. The modulation of these factors provides molecular insights of the anti-inflammatory action of CR in relation to the aging process. Based on available finding and our recent supporting evidence, we prefer to use "molecular inflammation" to emphasize the importance of the molecular reaction mechanisms and their aberrance, predisposing to fully expressed chronic inflammatory phenomena. It was further proposed that CR's major force of the regulation of redox-sensitive inflammation may well be its life-prolonging action.
Chung
Hae Young
HY
College of Pharmacy, Pusan National University, Pusan 609-735, Korea. hyjung@pusan.ac.kr
Kim
Hyon Jeen
HJ
Kim
Kyu Won
KW
Choi
Jae Sue
JS
Yu
Byung Pal
BP
D000375:Aging / Q000378:metabolism; D000818:Animals; D031204:Caloric Restriction; D002268:Carboxypeptidases; D043422:Carboxypeptidases A; D002352:Carrier Proteins / Q000502:physiology; D016207:Cytokines / Q000502:physiology; D005938:Glucocorticoids / Q000494:pharmacology; D006801:Humans; D007249:Inflammation / Q000378:metabolism*; D016328:NF-kappa B / Q000502:physiology; D019001:Nitric Oxide Synthase / Q000502:physiology; D052247:Nitric Oxide Synthase Type II; D018384:Oxidative Stress; D017382:Reactive Oxygen Species / Q000378:metabolism
D002352:Carrier Proteins; D016207:Cytokines; D005938:Glucocorticoids; D016328:NF-kappa B; D017382:Reactive Oxygen Species; C496319:NOS2 protein, human; D019001:Nitric Oxide Synthase; D052247:Nitric Oxide Synthase Type II; D002268:Carboxypeptidases; C115512:Cpxm2 protein, mouse; D043422:Carboxypeptidases A