Age-related evolution of human gingiva towards a fibrotic-like connective phenotype

Periodontal disease affects most adults over 50, but the role of aging in periodontal homeostasis remains poorly understood. This study examines variations in human gingival gene expression over time using transcriptomic and histological approaches. Results show a global decline in gene expression with age, suggesting a loss of genetic information that could weaken the gingiva’s ability to respond to stressors. The findings experimentally validate the SIM (Structure, Immunity, Metabolism) paradigm, emphasizing the central role of structural components in aging. Structural changes, including reduced collagen III signaling and decreased periostin levels, indicate impaired matrix remodeling as a key feature of gingival aging. These insights mark an important step toward defining biological age at the gingival level and improving risk assessment for periodontal diseases. This research lays the foundation for predictive and preventive strategies in periodontal medicine, aiming to enhance personalized interventions and early treatments to mitigate aging-related oral health decline.