New frontier for epilepsy treatment through targeting cellular senescence

Epilepsy is a life-threatening brain disorder that affects about 1–2 % of the world's population. Various mechanisms facilitating epilepsy development and seizure propagation have been identified. Nevertheless, an improved understanding of the cellular mechanisms that underlie epilepsy development is necessary for designing better therapeutic strategies for epilepsy treatment. Cellular senescence, a cellular mechanism wherein cell growth is permanently halted and causes cells to exit the proliferative pool, has been associated with neurological disorders such as multiple sclerosis, Alzheimer's disease, Parkinson's disease, and epilepsy. How the various mechanisms that drive a cell towards senescence and the phenotypes that characterize senescent cells are associated with the development and progression of epilepsy might be necessary in improving our understanding of epilepsy. Therefore, this review discusses the mechanisms and pathways associated with cellular senescence and how senescence-associated secretory phenotype (SASP) promotes inflammation and tissue dysfunction. We then explained how different types of cells, including brain cells, become senescent, the inter-relationship between cellular senescence and epilepsy, and potential biomarkers common to epilepsy and cellular senescence. Finally, we reviewed the use of senolytics and senomorphics for epilepsy treatment. Further research can, therefore, be directed towards a thorough understanding of cellular senescence in epilepsy development, and this can open new frontiers for epilepsy treatment. © 2025 The Authors