Zhang Ping, Cui Yu, Li Zekun, Liu Luyun, Liu Xinjuan, Ding Xiaoling, Ding Gang
School of Stomatology, Shandong Second Medical University, Baotong West Street No. 7166, Weifang, 261053, Shandong, China.
Clinical Competency Training Center, Shandong Second Medical University, Baotong West Street No. 7166, Weifang, 261053, Shandong, China.
Hum Cell. 2025 Jul 11;38(5):127. doi: 10.1007/s13577-025-01259-y.
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.
牙髓干细胞（DPSCs）是一类具有自我更新能力和多向分化潜能的成体干细胞，广泛应用于组织工程和再生医学领域。然而，随着供体年龄的增加或体外培养时间的延长，DPSCs逐渐表现出衰老相关的表型，包括增殖能力降低和分化潜能受损。本综述全面总结了DPSCs衰老研究的当前进展。首先，探讨了衰老的牙髓微环境如何影响DPSCs的生物学特性。然后，重点关注DPSCs衰老与线粒体功能障碍、表观遗传改变以及p53/p21/p16等关键信号通路之间的相互作用。在此基础上，讨论了近期延缓DPSCs衰老的分子策略，如褪黑素可通过抑制基质金属蛋白酶的表达减轻DPSCs衰老，二甲双胍可通过AMPK/mTOR信号通路干扰DPSCs衰老等。最后，对DPSCs、骨髓间充质干细胞和脂肪间充质干细胞的衰老特征进行了比较分析，以阐明这些细胞类型的独特特征和共同特征。总的来说，本综述可为推进基于DPSCs的再生应用中的抗衰老策略提供理论基础和实践见解。
