SCN9A gene therapy: Novel mechanism to inhibit cellular senescence in astrocytes in vitro

Cellular aging, also known as senescence, is a form of proliferation arrest that occurs in cells with age. In individuals, this process occurs due to telomere degradation and consequent dysfunction. In the nervous system, senescence of astrocytes, the most common neuronal support cells, has been associated with inflammation and forms of neurodegeneration associated with various disease pathologies. Thus, studying senescence may be a unique approach to understanding brain and aging and consequential diseases as well. Studies have shown that transcription downregulation of SCN9A led to reversal of senescence in epithelial cells. So, this study explores the role of SCN9A in astrocytes. In silico patient gene analysis reveals multiple significant pathways associated with neuronal aging including ion channel regulation. Subsequent analysis shows the downregulation of SCN9A is associated with genes in the neuronal senescence pathway. In vitro studies showed that astrocytes with knockdowned SCN9A did not undergo senescence as significantly as regular astrocytes. Furthermore, protein analysis presented a novel role for SCN9A in the astrocyte senescence pathway and an association with preventing DNA leakage. This study suggests SCN9A plays a large role in neurodegeneration and it should be studied in reversing senescence and even treatment plans for brain aging.