Research Square · Aug 4, 2022
Human Alpha 1 Antitrypsin Suppresses NF-ĸB Activity and Extends Lifespan in Adult Drosophila
By Yuan Y, Van Belkum M, O’Brien A et al.
Abstract Human alpha 1 antitrypsin (hAAT) is a multifunctional protein, which 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, which indicated that NF-ĸB-targeted genes and NF-ĸB-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-ĸB. Subsequently, hAAT treatment suppressed the mRNA levels of NF-ĸB targeted genes, as well as NF-ĸB itself (P65 and P50) in human senescent cells. Using Drosophila 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 late stage of life significantly extended the lifespan of transgenic flies. These results extended the current understandings of the anti-inflammation function of hAAT.