Lung cancer remains the leading cause of cancer death worldwide, and its burden is increasingly concentrated in older adults. As populations age, more people are developing lung adenocarcinoma later in life, yet the biological effects of aging on tumor behavior are only beginning to be understood. Aging lungs exist in a fundamentally altered state, shaped by chronic inflammation and the accumulation of senescent cells that release potent signaling molecules. These age-related changes may quietly reprogram normal lung cells long before cancer forms, influencing which cells become malignant and how aggressively tumors evolve. However, most cancer research and clinical trials fail to capture this reality, relying instead on young or artificially aged models. Understanding how aging itself reshapes lung tissue and cancer risk is therefore a pressing challenge, with major implications for prevention, disease progression, and treatment in the rapidly growing population of older lung cancer patients.
This project will investigate how aging-associated inflammation and cellular senescence alter the fate of lung epithelial cells to promote tumor evolution. Focusing on alveolar type 2 cells, which are the cell of origin for lung adenocarcinoma, the study will examine how pro-inflammatory signals drive a highly plastic cell state that enables malignant progression. Using spatial transcriptomics, single-cell analyses, and physiologically aged mouse models, the research will map age-specific cell–cell communication networks between senescent cells, immune cells, and emerging tumor populations. Functional perturbations such as senolytic treatments, anti-inflammatory interventions, and genetic ablation of plastic tumor states will directly test how these aging-related signals influence tumor growth. By integrating human and mouse data, this work will define how inflammaging shapes cancer evolution and identify intervention points that could slow or prevent lung cancer progression in older individuals.