Bridging aging and colorectal cancer: synergistic roles of inflammaging and immunosenescence.

Colorectal cancer (CRC) is one of the most commonly occurring malignancies worldwide, with incidence and mortality rising sharply in older adults. While aging is increasingly recognized as a key risk factor for CRC, the fundamental immunological mechanisms which underlie this risk remain incompletely understood. Two interconnected processes, namely inflammaging and immunosenescence, appear central to this association. On the one hand, inflammaging, which is characterized by chronic low-grade inflammation in older individuals, fosters a tumor-promoting microenvironment through oxidative stress, genomic instability, and persistent cytokine activation. On the other hand, immunosenescence diminishes immune surveillance, reducing the clearance of premalignant cells and weakening responses to tumor progression and therapy. Together, these processes create an immunological framework that predisposes the aging colon to malignant transformation. This review synthesizes current knowledge of the cellular and mechanistic impacts of inflammaging and immunosenescence in CRC pathogenesis, highlighting their roles in shaping disease susceptibility in the elderly. These insights may guide future endeavor in biomarker discovery, prevention, and therapeutic intervention to mitigate the burden of CRC in aging populations.