Xu Fangxi, Guo Yuqi, Thomas Scott C, Saxena Anish, Hwang Samantha, Vardhan Mridula, Li Xin
Department of Molecular Pathobiology, New York University College of Dentistry, New York, NY, USA.
Plastic Surgery, Maxillofacial and Oral Health Department, University of Virginia School of Medicine, Charlottesville, VA, USA.
Int J Oral Sci. 2025 Jun 10;17(1):47. doi: 10.1038/s41368-025-00376-6.
Aging involves the accumulation of various forms of molecular and cellular damage over time. Key features of aging, such as mitochondrial dysfunction, dysbiosis, and oxidative stress, are closely linked and largely driven by inflammation. This study examines the role of succinate, a key metabolite produced and utilized by cells of both host and microbes, and its receptor, succinate receptor 1 (SUCNR1), in age-related oral dysbiosis and inflammation. We examined young and aged wild-type (WT) and SUCNR1 knockout (KO) mice for this analysis. Our findings revealed significant aging-associated alveolar bone loss and succinate elevation in aged WT mice, along with notable changes in the oral microbiome. Conversely, aged KO mice showed reduced bone loss, lower succinate levels, less inflammation, and better-maintained microbial function. These results suggest that SUCNR1 is crucial in influencing aging-related succinate elevation, oral dysbiosis, and inflammation. Analysis of gene families and pathways in the oral microbiome demonstrated distinct aging-related changes between WT and KO mice, with the functional potential being preserved in the KO-aged group. This study underscores the importance of succinate elevation and signaling through SUCNR1 in regulating inflammation, alveolar bone loss, and shifts in the oral microbiome, offering potential targets for therapeutic interventions in age-related oral health issues.
衰老涉及随着时间推移各种分子和细胞损伤的积累。衰老的关键特征，如线粒体功能障碍、微生物群落失调和氧化应激，紧密相连且在很大程度上由炎症驱动。本研究考察了琥珀酸（一种宿主和微生物细胞均产生和利用的关键代谢物）及其受体琥珀酸受体1（SUCNR1）在与年龄相关的口腔微生物群落失调和炎症中的作用。我们为此分析检测了年轻和年老的野生型（WT）及SUCNR1基因敲除（KO）小鼠。我们的研究结果显示，年老的WT小鼠存在与衰老相关的显著牙槽骨丢失和琥珀酸水平升高，同时口腔微生物群也有明显变化。相反，年老的KO小鼠骨丢失减少、琥珀酸水平降低、炎症减轻且微生物功能维持得更好。这些结果表明，SUCNR1在影响与衰老相关的琥珀酸升高、口腔微生物群落失调和炎症方面至关重要。对口腔微生物群中基因家族和通路的分析表明，WT和KO小鼠之间存在与衰老相关的明显差异，而KO老年组的功能潜力得以保留。本研究强调了琥珀酸升高和通过SUCNR1的信号传导在调节炎症、牙槽骨丢失和口腔微生物群变化中的重要性，为与年龄相关的口腔健康问题的治疗干预提供了潜在靶点。
