Yu Zhuo-Wei, Bao Zhi-Jun, Ruan Qing-Wei, Ma Yong-Xing
Central Laboratory; Aging, Anti-aging and Cognitive Function Laboratory, Shanghai Institute of Geriatrics and Gerontology, Huadong Hospital, Shanghai Medical College, Fudan University, Shanghai 200040, China. E-mail:
Sheng Li Xue Bao. 2013 Jun 25;65(3):338-46.
The lifelong exposure of antigens and stressors results in chronic oxidative stress situation in the organism. The free radicals and reactive oxygen species (ROS) with high reactivity produced by our cells under oxidative stress will cause oxidative damage in biomolecules. The oxidative damage leads to the releases of both damage-associated-molecular patterns (DAMPs) and intracellular cytokines. DAMPs activate pathogen recognition receptors (PRRs) and non-PRRs. Intracellular cytokines activate signalling pathways downstream of PRRs. Activation of these receptors results in the upregulation of cytokines and chemokines, which are released to recruit and activate additional inflammatory cells and cause the systemic and chronic sterile inflammation. The regulatory system, especially immune systems play an important role in homeostasis maintenance in the organism. The cells of immune systems are very vulnerable to oxidative damage. Once the homeostasis is destroyed, an imbalance between inflammatory and anti-inflammatory networks will occur. Genetic factor also is an important factor of oxi-inflamm-aging and age-related diseases. Many genes are involved in oxidative stress, inflammation process, and the genomic variations within most of these genes might produce different effects on oxi-inflamm-aging. The polymorphism of ApoE genes can affect the antioxidant and immunomodulatory/anti-inflammatory properties of the organism. ApoE genotype-phenotype is associated with the progress and prognosis of oxi-inflamm-aging, age-related diseases as well. Anti-inflammation together with regulation of the expression of ApoE might be an efficient method against oxi-inflamm-aging. Based on our previous studies, the progresses in these areas are reviewed.
抗原和应激源的终身暴露会导致机体出现慢性氧化应激状态。我们的细胞在氧化应激下产生的具有高反应性的自由基和活性氧（ROS）会对生物分子造成氧化损伤。氧化损伤会导致损伤相关分子模式（DAMPs）和细胞内细胞因子的释放。DAMPs会激活病原体识别受体（PRRs）和非PRRs。细胞内细胞因子会激活PRRs下游的信号通路。这些受体的激活会导致细胞因子和趋化因子的上调，它们被释放出来以募集和激活更多的炎症细胞，并引发全身性和慢性无菌性炎症。调节系统，尤其是免疫系统在维持机体的内环境稳定中发挥着重要作用。免疫系统的细胞非常容易受到氧化损伤。一旦内环境稳定被破坏，炎症和抗炎网络之间就会出现失衡。遗传因素也是氧化-炎症-衰老及与年龄相关疾病的一个重要因素。许多基因都参与氧化应激、炎症过程，并且这些基因中的大多数基因的基因组变异可能会对氧化-炎症-衰老产生不同的影响。载脂蛋白E（ApoE）基因的多态性会影响机体的抗氧化以及免疫调节/抗炎特性。ApoE基因型-表型也与氧化-炎症-衰老、与年龄相关疾病的进展和预后相关。抗炎以及调节ApoE的表达可能是对抗氧化-炎症-衰老的一种有效方法。基于我们之前的研究，对这些领域的进展进行综述。
