Molecular inflammation hypothesis of aging based on the anti-aging mechanism of calorie restriction
Molecular inflammation hypothesis of aging based on the anti-aging mechanism of calorie restriction
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DOI：
10.1002/jemt.10203
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发表时间：
2002-11-15
影响因子：
2.5
通讯作者：
Yu, BP
中科院分区：
文献类型：
--
作者：
Chung, HY;Kim, HJ;Yu, BP
越来越多的证据强烈表明氧化应激是衰老过程的基础。研究提供了一致的证据，表明热量限制 (CR) 可减少与年龄相关的氧化应激并具有抗炎特性。然而，缺乏关于更好地定义活性氧和氮物种之间的相互关系以及衰老过程的促炎症状态的分子机制的信息。本文对衰老过程中炎症过程的生化和分子基础进行了分析，以阐明衰老的分子炎症假说。该假设中涉及的关键因素是与年龄相关的 NF-κB、IL-1β、IL-6、TNFα、环氧合酶-2 和诱导型 NO 合酶的上调，所有这些都会被 CR 减弱。此外，年龄相关的 NFκB 激活与 IκB 激酶/NIK 和 MAPK 的磷酸化有关，而 CR 则阻断这些激活过程。这些因素的调节提供了 CR 抗炎作用与衰老过程相关的分子见解。根据现有的发现和我们最近的支持证据，我们更喜欢使用“分子炎症”来强调分子反应机制及其异常的重要性，易于充分表达慢性炎症现象。进一步提出，CR 调节氧化还原敏感炎症的主要力量很可能是其延长生命的作用。显微镜。资源。技术。 59:264–272, 2002。© 2002 Wiley-Liss, Inc.
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‐κB, IL‐1β, IL‐6, TNFα, cyclooxygenase‐2, and inducible NO synthase, all of which are attenuated by CR. Furthermore, age‐related NFκB activation is associated with phosphorylation by IκB 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. Microsc. Res. Tech. 59:264–272, 2002. © 2002 Wiley‐Liss, Inc.