Inhibiting Cell Inspection Points Intervention Via Injectable Short Fibers for Reversing Neural Cell Senescence

Abstract

Neural cell senescence hinders spinal cord nerve function recovery, and existing therapies that target senescent cell clearance haven’t effectively addressed cellular senescence. In this study, injectable short fibers that accurately maintain genome homeostasis in real time were developed, which for the first time reversed neural cell senescence by blocking the excessive intervention of cell inspection points. First, the oxidization-sensitive hybrid liposomes were prepared by combining Bakuchiol (BAK), a natural plant extract with the ability of DNA protection, with the oxidization-sensitive phospholipid S-PC. Subsequently, the short fibers regulating the cell inspection points (ISN@n-BAK) were constructed by further complexing the oxidation-sensitive hybrid liposomes with short fibers through π–π conjugation and catechol groups mussel-stimulated polydopamine (PDA). In vitro experiments demonstrated that ISN@n-BAK promotes neural stem cell differentiation into neurons and has anti-aging effects across various aging stages. In vivo, ISN@n-BAK responded to excessive ROS by triggering oxidation-sensitive liposomes to release BAK, protecting against DNA damage, suppressing aging-related gene expression in Cdkn2a and Cdkn2c and inhibiting inspection point restrictions. Bioinformatics showed that ISN@n-BAK reversed neural cell senescence and aided spinal cord nerve regeneration by activating the endogenous cell cycle, downregulating the PI3K-Akt pathway and upregulating the Rap1 pathway. This study introduces a novel therapeutic approach using short fibers that inhibit inspection points intervention to rejuvenate injured spinal cords.

Graphical Abstract

Keywords

Neural cell senescence / Inspection point / Short fibers / Spinal cord

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Funding

National Nature Science Foundation of China(32000937)

Science and Technology Commission of Shanghai Municipality(23015820800)

RIGHTS & PERMISSIONS

Donghua University, Shanghai, China