Aging and senescence: Key players in brain tumor progression and drug resistance

Abstract

Aging plays a critical role in the development, progression, and therapeutic challenges associated with brain tumors, particularly glioblastomas (GBM). As the population ages, the incidence of brain tumors, including GBM, increases, with aging emerging as a significant prognostic factor influencing survival outcomes. This review examines the molecular mechanisms linking aging and brain tumor progression, with a specific focus on glioblastomas. We explore how age-related genetic mutations, alterations in cellular pathways, and changes in the tumor microenvironment (TME) contribute to tumorigenesis and treatment resistance. Furthermore, we highlight the impact of key signaling pathways, such as the PI3K/AKT/mTOR, p53, and EGFR/PTEN, which are frequently dysregulated in both aging and brain tumors. Despite the growing recognition of aging as a critical factor in brain tumor biology, therapeutic strategies for elderly patients remain poorly defined, often due to underrepresentation in clinical trials and the complex interplay of comorbidities and treatment side effects. The review also discusses emerging therapeutic approaches, including targeted therapies and immunotherapies, which offer promise for improving treatment outcomes by addressing age-related molecular changes. Finally, we emphasize the importance of personalized treatment strategies and the need for further research to better understand the biological mechanisms underlying the aging-brain tumor relationship, ultimately aiming to enhance clinical management and patient quality of life.