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.

© 2025. The Author(s).

衰老涉及随着时间的推移在分子和细胞水平上累积各种形式的损伤。衰老的关键特征，如线粒体功能障碍、菌群失调和氧化应激，彼此密切相关，并且主要由炎症驱动。本研究考察了琥珀酸盐（一种宿主细胞和微生物产生的关键代谢物）及其受体琥珀酸受体1 (SUCNR1) 在与年龄相关的口腔菌群失调和炎症中的作用。我们对年轻和年老的野生型 (WT) 和 SUCNR1 敲除 (KO) 小鼠进行了分析。我们的研究结果揭示了老年 WT 小鼠中显著的老龄相关牙槽骨丧失和琥珀酸水平升高，以及口腔微生物群的明显变化。相反，老年 KO 小鼠表现出较少的骨质流失、较低的琥珀酸水平、更少的炎症，并且维持更好的微生物功能。这些结果表明 SUCNR1 在影响与年龄相关的琥珀酸水平升高、口腔菌群失调和炎症方面起着关键作用。对口腔微生物组中的基因家族和途径进行分析，发现 WT 和 KO 小鼠之间存在明显的衰老相关变化，在 KO 老年组中保持了功能潜力。这项研究强调了通过 SUCNR1 信号传导调控琥珀酸水平升高、牙槽骨流失以及口腔菌群的变化的重要性，并为年龄相关的口腔健康问题提供了潜在的治疗靶标。

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