Cellular Senescence in Periodontal Ageing: Molecular Mechanisms, Clinical Implications and Emerging Therapeutic Strategies

Abstract

Cellular senescence is increasingly recognised as an important biological process associated with ageing-related tissue dysfunction. In periodontal tissues, senescence may contribute to impaired cellular turnover, reduced regenerative capacity, chronic inflammation, and increased susceptibility to periodontal destruction. Senescent cells are characterised by stable cell-cycle arrest and the production of a senescence-associated secretory phenotype, which includes pro-inflammatory cytokines, chemokines, matrix-degrading enzymes, and growth factors. These mediators may influence the periodontal microenvironment by promoting extracellular matrix degradation, osteoclast activation, altered immune responses, and delayed tissue repair. This review summarises current evidence on the role of cellular senescence in periodontal ageing, with emphasis on molecular mechanisms, tissue-specific effects, clinical implications, and emerging therapeutic strategies. Key mechanisms discussed include telomere attrition, oxidative stress, DNA damage responses, mitochondrial dysfunction, and activation of p53–p21 and p16INK4a–retinoblastoma signalling pathways. The review also considers the contribution of senescent gingival fibroblasts, periodontal ligament cells, osteoblasts, cementoblasts, and mesenchymal stem cells to age-associated periodontal changes. Available evidence suggests that cellular senescence may contribute to a bidirectional relationship between ageing and periodontitis, in which chronic periodontal inflammation promotes senescence while senescent cells further amplify inflammatory tissue damage. Emerging approaches such as senolytics, senomorphics, stem-cell-based therapy, exosome-based therapy, and gene or epigenetic modulation are being investigated as potential strategies to improve periodontal regeneration and reduce senescence-associated dysfunction. However, most evidence remains preclinical, and further well-designed human studies are required before senescence-targeted interventions can be translated into routine periodontal practice.