Chung Hun Taeg, Joe Yeonsoo
School of Biological Sciences, University of Ulsan, Ulsan, Korea.
Integr Med Res. 2014 Dec;3(4):198-203. doi: 10.1016/j.imr.2014.09.005. Epub 2014 Oct 2.
Current studies have indicated the association of chronic sterile inflammation (inflammation in the absence of pathogens) with the pathogenesis of age-related and metabolic diseases. The inflammation is under the control of transcription factor NF-κB through an antagonistic crosstalk between SIRT1, PARP-1, and -2 signaling pathways. The transcriptional activity of NF-κB is increased in various tissues with aging and metabolic abnormalities and is related with various aging and metabolic diseases such as Alzheimer's disease, diabetes, and osteoporosis. Furthermore, NF-κB activation with chronic inflammation is connected with many known life span and metabolic regulators including DNA damage, obesity, SIRT, and PARP. Thus, the crossroads between PARP and SIRT signaling pathways represent efficient therapeutic targets for extending health span without metabolic diseases.
目前的研究表明，慢性无菌性炎症（无病原体存在时的炎症）与年龄相关性疾病和代谢性疾病的发病机制有关。这种炎症受转录因子NF-κB的控制，通过SIRT1、PARP-1和-2信号通路之间的拮抗相互作用来实现。随着衰老和代谢异常，NF-κB的转录活性在各种组织中增加，并与多种衰老和代谢性疾病相关，如阿尔茨海默病、糖尿病和骨质疏松症。此外，慢性炎症引起的NF-κB激活与许多已知的寿命和代谢调节因子有关，包括DNA损伤、肥胖、SIRT和PARP。因此，PARP和SIRT信号通路的交叉点代表了在不引发代谢性疾病的情况下延长健康寿命的有效治疗靶点。
