Department of Pharmaceutics, College of Pharmacy, University of Florida, Gainesville, FL 32610, USA.
L&L Biotechnology, Gainesville, FL 32610, USA.
Biomolecules. 2022 Sep 22;12(10):1347. doi: 10.3390/biom12101347.
Human alpha 1 antitrypsin (hAAT) is a multifunctional protein that has been shown to have anti-inflammatory and cellular protective properties. While previous studies demonstrated the antiaging potential of hAAT, the mechanism(s) underlying the antiaging effect remain elusive. In this study, we performed a detailed analysis of transcriptomic data that indicated that NF-κB-targeted genes and NF-κB-regulated pathways were selectively inhibited by hAAT treatment. We further showed that the first detectable impact of hAAT treatment was the inhibition of the nuclear activity of NF-κB. Subsequently, hAAT treatment suppressed the mRNA levels of NF-κB-targeted genes, as well as itself ( and ), in human senescent cells. Using models, we further examined the impact of hAAT on locomotor activity and endurance. Finally, using an adult-specific promotor, we demonstrated that overexpression of hAAT in the late stage of life significantly extended the lifespan of transgenic flies. These results extend the current understanding of the anti-inflammatory function of hAAT.
人血清白蛋白（hAAT）是一种多功能蛋白，具有抗炎和细胞保护特性。虽然先前的研究表明 hAAT 具有抗衰老潜力，但抗衰老作用的机制仍不清楚。在这项研究中，我们对转录组数据进行了详细分析，表明 hAAT 治疗选择性抑制 NF-κB 靶向基因和 NF-κB 调节途径。我们进一步表明，hAAT 治疗的第一个可检测影响是抑制 NF-κB 的核活性。随后，hAAT 治疗抑制了人衰老细胞中 NF-κB 靶向基因以及自身（ 和 ）的 mRNA 水平。使用 模型，我们进一步研究了 hAAT 对运动活性和耐力的影响。最后，使用一种成人特异性启动子，我们证明了在生命晚期过表达 hAAT 可显著延长转基因果蝇的寿命。这些结果扩展了对 hAAT 抗炎功能的现有认识。
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