Chuang Shih-Yi, Lin Chih-Hung, Fang Jia-You
Pharmaceutics Laboratory, Graduate Institute of Natural Products, Chang Gung University, 259 Wen-Hwa 1st Road, Kweishan, Taoyuan 333, Taiwan ; Research Center for Industry of Human Ecology, Chang Gung University of Science and Technology, Kweishan, Taoyuan 333, Taiwan.
Center for General Education, Chang Gung University of Science and Technology, Kweishan, Taoyuan 333, Taiwan ; Chronic Diseases and Health Promotion Research Center, Chang Gung University of Science and Technology, Kweishan, Taoyuan 333, Taiwan.
Biomed Res Int. 2014;2014:297293. doi: 10.1155/2014/297293. Epub 2014 Sep 14.
Aging, a natural physiological process, is characterized by a progressive loss of physiological integrity. Loss of cellular homeostasis in the aging process results from different sources, including changes in genes, cell imbalance, and dysregulation of the host-defense systems. Innate immunity dysfunctions during aging are connected with several human pathologies, including metabolic disorders and cardiovascular diseases. Recent studies have clearly indicated that the decline in autophagic capacity that accompanies aging results in the accumulation of dysfunctional mitochondria, reactive oxygen species (ROS) production, and further process dysfunction of the NACHT, LRR, and PYD domains-containing protein 3 (NLRP3) inflammasome activation in the macrophages, which produce the proinflammatory cytokines. These factors impair cellular housekeeping and expose cells to higher risk in many age-related diseases, such as atherosclerosis and type 2 diabetes. In this review, we investigated the relationship between dysregulation of the inflammasome activation and perturbed autophagy with aging as well as the possible molecular mechanisms. We also summarized the natural compounds from food intake, which have potential to reduce the inflammasome activation and enhance autophagy and can further improve the age-related diseases discussed in this paper.
衰老作为一种自然生理过程,其特征是生理完整性逐渐丧失。衰老过程中细胞内稳态的丧失源于多种因素,包括基因变化、细胞失衡以及宿主防御系统失调。衰老过程中的先天免疫功能障碍与多种人类疾病相关,包括代谢紊乱和心血管疾病。最近的研究清楚地表明,衰老过程中自噬能力的下降导致功能失调的线粒体积累、活性氧(ROS)生成,进而导致巨噬细胞中含NACHT、LRR和PYD结构域蛋白3(NLRP3)炎性小体激活的进一步过程功能障碍,而巨噬细胞会产生促炎细胞因子。这些因素损害细胞内环境稳定,使细胞在许多与年龄相关的疾病(如动脉粥样硬化和2型糖尿病)中面临更高风险。在本综述中,我们研究了炎性小体激活失调和自噬紊乱与衰老之间的关系以及可能的分子机制。我们还总结了食物中的天然化合物,它们有可能减少炎性小体激活并增强自噬,进而改善本文讨论的与年龄相关的疾病。