A Novel Strategy to Model Age-Related Cancer for Elucidation of the Role of Th17 Inflammaging in Cancer Progression

SIMPLE SUMMARY: Cancer is a disease of aging, but how aging contributes to cancer remains unclear. A mouse model of cancer that allows the spatially and temporally controlled initiation of tumors is critical to understanding the molecular mechanisms of the complex processes and related gene pathways of biological aging that play a role in cancer initiation and progression. One of the hallmarks of aging is chronic inflammation, often called inflammaging. We have implicated aging-related inflammation in prostate cancer, a major aging malignancy. We present our novel strategy for the generation of age-related cancer models in mice and discuss how we use these prostate cancer mouse models, generated at different ages, to elucidate mechanisms contributing to development of tumors during aging. ABSTRACT: Cancer is a disease of aging, but most studies on cancer are in young but not aged animal models, and cancer clinical trials are rarely performed in older adults. Recognition of the connections between aging and cancer and improvement of treatment for elderly cancer patients has become one of the most critical medical issues with the global increase in the elderly population. Mouse models are essential experimental tools for understanding the molecular mechanisms of complex processes and related gene pathways of biological aging. However, few mouse models can be used to understand the role of aging in cancer development and the underlying mechanisms. One of the hallmarks of aging is chronic inflammation, often called inflammaging. This is our rationale for examining the role of aging-related inflammation in prostate cancer, a major aging malignancy. We have now developed a novel method to generate age-related cancer models in mice to better understand how age impacts cancer initiation and progression in the natural aging process. We discuss its application to elucidate some of the contributing mechanisms.