Advanced Age in Humans and Mouse Models of Glioblastoma Show Decreased Survival from Extratumoral Influence

Purpose: Glioblastoma (GBM) is the most common aggressive mice with or without a brain tumor. The survival of young and old primary malignant brain tumor in adults with a median age of onset wild-type or transgenic (INK-ATTAC) mice with a brain tumor was of 68 to 70 years old. Although advanced age is often associated with evaluated after treatment with or without senolytics and/or poorer GBM patient survival, the predominant source(s) of malimmunotherapy. adaptive aging effects remains to be established. Here, we studied Results: Human patients with GBM ≥65 years of age had a ntratumoral and extratumoral relationships between adult patients significantly decreased survival compared with their younger with GBM and mice with brain tumors across the lifespan. counterparts. While the intra-GBM molecular profiles were simExperimental Design: Electronic health records at Northwestern ilar between younger and older patients with GBM, non-tumor Medicine and the NCI SEER databases were evaluated for GBM brain tissue had a significantly different gene expression profile patient age and overall survival. The commercial Tempus and Caris between young and old mice with a brain tumor and the eradidatabases, as well as The Cancer Genome Atlas were profiled for cation of senescent cells improved immunotherapy-dependent gene expression, DNA methylation, and mutational changes with survival of old but not young mice. varying GBM patient age. In addition, gene expression analysis was Conclusions: This work suggests a potential benefit for com-performed on the extratumoral brain of younger and older adult bining senolytics with immunotherapy in older patients with GBM.