NF-κB in Aging and Disease.
NF-κB in Aging and Disease.
复制标题
DOI：
--
复制
发表时间：
2011-06
影响因子：
7.4
通讯作者：
J. Tilstra;Cheryl L. Clauson;L. Niedernhofer;P. Robbins
中科院分区：
文献类型：
--
作者：
J. Tilstra;Cheryl L. Clauson;L. Niedernhofer;P. Robbins
细胞大分子和细胞器的随机损伤被认为是衰老和相关退行性变化背后的驱动力。然而，这种损伤激活的应激反应途径也可能导致衰老。IKK/NF-κB信号通路被认为是衰老的关键介质之一。它被遗传毒性、氧化和炎症应激激活，并调节细胞因子、生长因子和调节细胞凋亡、细胞周期进程、细胞衰老和炎症的基因的表达。NF-κB的转录活性在多种组织中随着衰老而增加，并且与许多年龄相关的退行性疾病（包括阿尔茨海默氏病、糖尿病和骨质疏松症）相关。在小鼠模型中，NF-κB的抑制导致年龄相关症状和病理的延迟发作。此外，NF-κB活化与许多已知的寿命调节剂相关，包括胰岛素/IGF-1、FOXO、SIRT、mTOR和DNA损伤。因此，NF-κB代表了延长哺乳动物健康寿命的可能的治疗靶点。
Stochastic damage to cellular macromolecules and organelles is thought to be a driving force behind aging and associated degenerative changes. However, stress response pathways activated by this damage may also contribute to aging. The IKK/NF-κB signaling pathway has been proposed to be one of the key mediators of aging. It is activated by genotoxic, oxidative, and inflammatory stresses and regulates expression of cytokines, growth factors, and genes that regulate apoptosis, cell cycle progression, cell senescence, and inflammation. Transcriptional activity of NF-κB is increased in a variety of tissues with aging and is associated with numerous age-related degenerative diseases including Alzheimer's, diabetes and osteoporosis. In mouse models, inhibition of NF-κB leads to delayed onset of age-related symptoms and pathologies. In addition, NF-κB activation is linked with many of the known lifespan regulators including insulin/IGF-1, FOXO, SIRT, mTOR, and DNA damage. Thus NF-κB represents a possible therapeutic target for extending mammalian healthspan.