Leucokinin VIII acetate mitigates asthma severity by targeting ADCK5-induced cellular senescence.

Severe asthma poses a significant challenge in clinical management due to its poor responsiveness to conventional therapies and worse overall prognosis. Identifying differentially expressed genes (DEGs) between severe asthma and non-severe asthma, exploring potential therapeutic targets, and intervening in these targets could offer new strategies to overcome the treatment bottleneck in severe asthma and improve clinical outcomes. Bioinformatics analysis first revealed that DEGs between severe and non-severe asthma were predominantly enriched in the longevity-regulating pathway, which is closely linked to cellular senescence. Subsequent in vitro experiments confirmed a heightened level of cellular senescence in severe asthma. Notably, ADCK5 was identified as a highly expressed senescence-related marker in severe asthma, exhibiting both strong predictive value for the condition and a clear association with cellular senescence. Finally, through high-throughput compound screening, molecular docking, and experimental validation, Leucokinin VIII acetate (Leucokinin 8) was found to inhibit ADCK5 expression and reduce excessive cellular senescence. In summary, ADCK5 emerges as a critical gene involved in airway senescence in severe asthma, and Leucokinin 8 may offer therapeutic potential by targeting ADCK5 to alleviate airway senescence, thus improving severe asthma outcomes.