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

## TL;DR

This paper reviews how autophagy and cell senescence interact in glioblastoma, a deadly brain cancer in older people, and how these interactions could lead to new treatments.

## Contribution

The paper novelly focuses on the interplay between autophagy and senescence in glioblastoma pathogenesis and therapeutics.

## Key findings

- Autophagy and senescence have paradoxical roles in glioblastoma growth and suppression.
- Dysregulation of aging-related signaling pathways contributes to glioblastoma progression.
- Targeting autophagy and senescence could improve therapeutic outcomes in aging populations.

## Abstract

Glioblastoma (GBM) is the most common malignant tumor of the brain in the aging population.

The role of some of the aging hallmarks in the progression and suppression of GBM has been considered; however, the contribution of interactions among them has received less attention.

For this review, we analyze the role of the interplay between cellular senescence and autophagy in the paradoxical effects on GBM tumor growth and suppression with the corresponding therapeutic implications.

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.