Senescence of dental pulp stem cells: phenotypes, underlying mechanisms and regulatory molecules

Dental pulp stem cells (DPSCs) are a population of adult stem cells with self-renewal capacity and multilineage differentiation potential, widely utilized in tissue engineering and regenerative medicine. However, with increasing donor age or prolonged in vitro expansion, DPSCs gradually exhibit senescence-associated phenotypes, including reduced proliferative capacity and impaired differentiation potential. This review comprehensively summarizes current advances in the study of DPSCs senescence. First, it explores how the aging dental pulp microenvironment influences the biological characteristics of DPSCs. It then focuses on the interplay between DPSCs senescence and mitochondrial dysfunction, epigenetic alterations, as well as key signaling pathways such as p53/p21/p16. On this basis, recent molecular strategies for delaying DPSCs senescence are discussed, such as melatonin can alleviate DPSCs senescence by inhibiting the expression of matrix metalloproteinase, and metformin could interfere DPSCs senescence by AMPK/mTOR signaling pathway, etc. Lastly, a comparative analysis of senescence characteristics among DPSCs, bone marrow and adipose derived mesenchymal stem cells, is conducted to contextualize the unique and shared features of these cell types. Collectively, this review could provide a theoretical foundation and practical insights for advancing anti-senescence strategies in DPSC-based regenerative applications.