Cancer is often described as a disease of aging, yet we still lack a clear explanation for why tumors become so much more common later in life. One of the most striking changes that accompanies aging is the buildup of senescent cells, which are damaged cells that stop dividing but remain biologically active. While these cells have beneficial roles earlier in life, they gradually accumulate, contributing to age-related diseases. Emerging evidence suggests that senescent cells may also create fertile ground for cancer but proving this has been challenging due to artificial experimental systems that fail to capture true aging biology. As a result, we do not yet understand whether senescent cells actively drive tumor development, how they influence nearby pre-cancerous cells, or whether their presence could be exploited to identify or prevent cancer earlier. Addressing these gaps is essential for unraveling how aging itself fuels cancer risk.
This project will investigate how senescent cells shape the aged tissue environment to promote tumor initiation, with a particular focus on metabolism. Using fully age-matched mouse models and innovative senolytic CAR T cell therapies to selectively eliminate senescent cells in vivo, the research will directly test how senescent burden influences cancer development over time. Beyond inflammation, the study will dissect how senescent cells remodel local metabolic resources, such as nucleotide availability, which could confer premalignant clones a growth advantage. High-resolution metabolomics and stable isotope tracing will be used to map these metabolic interactions at unprecedented depth. Building on these mechanistic insights, the project will also explore senescent-derived metabolites as early biomarkers of tumorigenesis and evaluate senolytic CAR T cells as preventive and therapeutic interventions. Together, this work will redefine how aging biology is leveraged to detect, intercept, and treat cancer.