去乙酰化酶Sirtuin 1(Sirt1)作为抗衰老的新靶点被人们所重视。我们前期研究发现间充质细胞(MSC)过表达Sirt1增加小鼠的牙槽骨量，Bmi1基因敲除能阻断该变化。因此提出Sirt1通过去乙酰化Bmi1，促进其核转位，抑制Bmi1下游p16/p19和p53-ROS信号通路，从而促进MSC增殖和向成骨细胞分化，抑制其凋亡和衰老，发挥防治牙槽骨丢失的假说。我们拟利用小鼠表型分析，细胞、分子生物学等方法，证实MSC过表达Sirt1能防止衰老小鼠的牙槽骨丢失；Sirt1经Bmi1介导促牙槽骨形成；Sirt1可促进Bmi1的去乙酰化及核转位，抑制p16/p19和p53-ROS，促进MSC增殖和向成骨细胞分化，抑制其凋亡和衰老；Sirt1激活剂在抗牙槽骨丢失中的应用。本研究有望阐明Sirt1在抗老年性牙槽骨丢失中的作用机制，并为Sirt1激活剂白黎芦醇用于预防牙槽骨丢失提供理论和实验依据。

Sirtuin 1 (Sirt1), a protein deacetylase, is a novel target of anti-aging therapies. Our previous studies found that Sirt1 overexpression in Mesenchymal stem cells (MSCs) resulted in the increase of alveolar bone volume, which can be blocked by Bmi1 gene deletion. Therefore, we hypothesize that Sirt1 promotes MSC proliferation and differentiation into osteoblasts, but inhibits MSC senescence and apoptosis to prevent alveolar bone loss through promoting the deacetylation and nuclear translocation of Bmi1 to suppress the p16/p19 and p53-ROS signaling pathways. We will test this hypothesis at morphological, cellular and molecular levels. We will investigate that, 1) Sirt1 overexpression in MSCs prevents alveolar bone loss in aged mice; 2) Sirt1 regulates alveolar bone formation via Bmi1; 3) Sirt1 promotes MSC proliferation and differentiation into osteoblasts, but inhibits MSC senescence and apoptosis, through promoting the deacetylation and nuclear translocation of Bmi1 to suppress the p16/p19 and p53-ROS signaling pathways. 4) Sirt1 activator can be used to prevent the alveolar bone loss. Our study is going to elucidate the mechanism by which Sirt1 in preventing alveolar bone loss during aging and will advance the clinical applications of Sirt1 activator, resveratrol on preventing alveolar bone loss.