Role of the Interplay Between Autophagy and Cell Senescence in the Pathogenesis and Therapeutics of Glioblastoma in the Aging Population

Glioblastoma (GBM), formerly referred to as glioblastoma multiforme, represents the most prevalent and aggressive form of glioma, predominantly affecting the aging population. Despite considerable advances in recent years in elucidating its pathogenesis and developing novel immunotherapeutic approaches, the overall survival rate for patients with this central nervous system (CNS) neoplasm remains dismally low. Consequently, there is an urgent and unmet need to identify and characterize additional therapeutic targets that could be employed synergistically with existing treatment modalities to enhance both survival outcomes and quality of life. Among the emerging areas of investigation, substantial interest has been directed toward aging-associated molecular signaling mechanisms that also constitute key oncogenic pathways in GBM. These include aberrant growth factor signaling, hyperactivation of the PI3K/AKT/mTOR axis, and inactivation of critical tumor suppressor pathways such as p53 and retinoblastoma (RB). The dysregulation of these signaling cascades results in profound disturbances of essential cellular homeostatic processes, notably autophagy and cellular senescence, which are intimately involved in both tumor initiation and progression. This review aims to delineate the complex interplay between autophagy and cellular senescence within the context of aging-related GBM pathogenesis. Furthermore, it explores the relevant intracellular signaling transduction mechanisms that govern these processes and discusses prospective therapeutic strategies.