Oral mucosal ageing represents a fundamental reprogramming of the tissue microenvironment, a dynamic process that underlies the functional decline and heightened disease susceptibility observed in the elderly. This review synthesises current evidence to reconceptualise oral mucosal ageing as an active reprogramming of the tissue microenvironment, delineating the interplay between structural, molecular, and immunological changes, and exploring how these alterations drive functional decline and increase susceptibility to age-related oral diseases. Through a comprehensive analysis of experimental and clinical studies from human and animal models, we demonstrate that the ageing process fundamentally transforms the oral mucosa. Key findings include structural changes such as epithelial atrophy, extracellular matrix remodelling, and salivary gland degeneration, driven molecularly by genomic instability, accumulation of proinflammatory senescent cells, stem cell exhaustion, and dysregulated stress responses. These are compounded by an immunological state of ‘inflammaging’ and functional decline in innate and adaptive immunity, further exacerbated by shifts in the oral microbiome. Collectively, these deficits lead to impaired regeneration, diminished sensory function, and reduced salivary secretion, creating a permissive landscape for chronic oral diseases. In conclusion, oral mucosal ageing is a dynamic process of microenvironmental reprogramming driven by cellular senescence, immunosenescence, and structural decay. This actively underpins the heightened vulnerability to oral disease in the elderly, providing a mechanistic foundation for developing targeted interventions to preserve oral health in ageing populations.
Qiu et al. (Mon,) studied this question.