Integrated bioinformatics and molecular simulation identify PIM3 as a potential mediator of nicotine-associated skin aging

Smoking is a major extrinsic risk factor for skin aging, and nicotine, the primary bioactive component of tobacco, may play an important role in this process. However, the molecular mechanisms underlying nicotine-associated skin aging remain unclear. In this study, we integrated bioinformatics, transcriptomic analysis, weighted gene co-expression network analysis, machine learning, molecular docking, and molecular dynamics simulations to identify potential targets and pathways involved in nicotine-associated skin aging. Nicotine-related targets were predicted from multiple public databases, and skin aging-related genes were obtained from the GSE85358 dataset. A total of 24 potential targets were identified, among which three core genes, PIM3, FABP3, and MAPK8, were prioritized. Functional enrichment analysis indicated that these genes were mainly involved in kinase signaling, lipid metabolism, and stress-response pathways, including PI3K–Akt and PPAR signaling. Molecular docking showed that nicotine exhibited the strongest binding affinity with PIM3, and molecular dynamics simulation supported the stability of the PIM3–nicotine complex. These findings provide evidence suggesting that nicotine-associated skin aging may be related to dysregulation of kinase signaling, lipid metabolism, and stress-response pathways, with PIM3 as a potential key mediator. Further experimental validation is warranted.