首页 | 本学科首页   官方微博 | 高级检索  
   检索      


Anti‐inflammaging effects of human alpha‐1 antitrypsin
Authors:Ye Yuan  Benedetto DiCiaccio  Ying Li  Ahmed S Elshikha  Denis Titov  Brian Brenner  Lee Seifer  Hope Pan  Nurdina Karic  Mohammad A Akbar  Yuanqing Lu  Sihong Song  Lei Zhou
Institution:1. Department of Pharmaceutics, University of Florida, Gainesville, FL, USA;2. Department of Molecular Genetics & Microbiology, University of Florida, Gainesville, FL, USA;3. University of Florida Genetics Institute, Gainesville, FL, USA;4. UF Health Cancer Center, Gainesville, FL, USA
Abstract:Inflammaging plays an important role in most age‐related diseases. However, the mechanism of inflammaging is largely unknown, and therapeutic control of inflammaging is challenging. Human alpha‐1 antitrypsin (hAAT) has immune‐regulatory, anti‐inflammatory, and cytoprotective properties as demonstrated in several disease models including type 1 diabetes, arthritis, lupus, osteoporosis, and stroke. To test the potential anti‐inflammaging effect of hAAT, we generated transgenic Drosophila lines expressing hAAT. Surprisingly, the lifespan of hAAT‐expressing lines was significantly longer than that of genetically matched controls. To understand the mechanism underlying the anti‐aging effect of hAAT, we monitored the expression of aging‐associated genes and found that aging‐induced expressions of Relish (NF‐?B orthologue) and Diptericin were significantly lower in hAAT lines than in control lines. RNA‐seq analysis revealed that innate immunity genes regulated by NF‐kB were significantly and specifically inhibited in hAAT transgenic Drosophila lines. To confirm this anti‐inflammaging effect in human cells, we treated X‐ray‐induced senescence cells with hAAT and showed that hAAT treatment significantly decreased the expression and maturation of IL‐6 and IL‐8, two major factors of senescence‐associated secretory phenotype. Consistent with results from Drosophila,RNA‐seq analysis also showed that hAAT treatment significantly inhibited inflammation related genes and pathways. Together, our results demonstrated that hAAT significantly inhibited inflammaging in both Drosophila and human cell models. As hAAT is a FDA‐approved drug with a confirmed safety profile, this novel therapeutic potential may make hAAT a promising candidate to combat aging and aging‐related diseases.
Keywords:   Drosophila     human alpha‐1 antitrypsin  inflammaging  NF‐κ  B  innate immune response  senescence‐associated secretory phenotype
设为首页 | 免责声明 | 关于勤云 | 加入收藏

Copyright©北京勤云科技发展有限公司  京ICP备09084417号