Impact of aging on the tumor microenvironment in oral cancer: Mechanisms and therapeutic perspectives.

Oral cancer is a significant health problem worldwide, with particularly great impacts on elderly people. The aging process has a major impact on the tumor microenvironment (TME), affecting tumor initiation, progression, and the response to therapy. The present review summarizes the existing evidence regarding the effects of aging on the TME in oral cancer, the progression of oral diseases, and the implications for therapy. Studies were retrieved by conducting a structured literature search in the PubMed and MEDLINE databases from January 2010 to January 2025. Various age-related events such as cellular senescence, immunosenescence, extracellular matrix remodeling, chronic low-grade inflammation (inflammaging), and vascular dysfunction contribute to the creation of a pro-tumorigenic niche, which facilitates immune evasion and treatment resistance. The mechanisms of cellular senescence and immune deregulation, oxidative stress, and endothelial dysfunction are discussed in this review, as well as their roles in reducing anti-tumor immunity and therapeutic responses in elderly patients. Research shows that all of these age-related modifications are interconnected, and together they promote tumor progression and are involved in therapeutic resistance. Geriatric biology and TME research has highlighted new therapeutic approaches that could involve targeting senescence mechanisms, immune modulation, and vessel aging. Further insights into age-related TME dynamics are needed to develop aging-focused, tailored interventions that can enhance clinical results in older individuals with oral cancer.