title: Molecular inflammation hypothesis of aging based on the anti-aging mechanism of calorie restriction.
abstract: 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.
authors.affiliation: College of Pharmacy, Pusan National University, Pusan 609-735, Korea. hyjung@pusan.ac.kr
authors.forename: Hae Young
authors.initials: HY
authors.lastname: Chung
authors.forename: Hyon Jeen
authors.initials: HJ
authors.lastname: Kim
authors.forename: Kyu Won
authors.initials: KW
authors.lastname: Kim
authors.forename: Jae Sue
authors.initials: JS
authors.lastname: Choi
authors.forename: Byung Pal
authors.initials: BP
authors.lastname: Yu
mesh_terms: 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
chemical_list: 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