环黄芪醇选择性清除衰老细胞及抑制SASP的抗衰老机制研究

我国已进入老龄化社会，衰老相关疾病严重威胁着人类健康。衰老细胞累积被认为是机体衰老的基础，其通过周期阻滞，凋亡抵抗和分泌SASP促进衰老及相关疾病的产生。通过清除衰老细胞或抑制SASP来阻断衰老细胞的促衰老作用成为防治老年性疾病的有效策略。然而，目前研究的大部分靶向衰老细胞的化合物在临床试验中受到诸多副作用的限制，急需研究和开发新的靶向药物。我们前期研究发现环黄芪醇（CAG）能够选择性清除衰老细胞并抑制SASP，其作用机制可能与下调Bcl-2家族抗凋亡蛋白,p38MAPK/NF-κB和JAK/STAT3信号通路有关。因此，本项目拟研究CAG对不同因素诱导的衰老细胞的清除和SASP的抑制作用，阐明CAG清除衰老细胞和抑制SASP的作用机制，并在衰老小鼠中进一步评价CAG的抗衰老作用。本项目将讨论CAG除激活端粒酶以外的抗衰老新靶点，为抗衰老药物的研究提供理论基础和科学依据。

China has entered an aging society which acompanied with numerous age-related diseases and functional decline that seriously threatening people's health．Senescent cells accumulate in various tissues and organs, promoteaging age-related diseases by replicative arrest, apoptosis resistance and secretion of SASP. Therefore, eliminating senescent cells or blocking the secretion of SASP are effective strategies for age-related diseases treatment. However, most of the compounds are currently limited in clinical trials, new targeted drugs development is urgent. We have screened a series of compounds and found that the cycloastragenol (CAG) can selectively eliminate senescent cells and inhibiting SASP. The mechanism may be related to the down-regulation of Bcl-2 family，p38MAPK/NF-κB and JAK/STAT3. This study is to investigate the elimination effect and inhibition SASP of senescent cells after CAG treatment in different senescent cells model and preliminary identify the mechanism of elimination and SASP inhibition effect of CAG. Finally, we will evaluate the anti-aging effects of the CAG in aging mouse model. In conclusion, this study may find a new target of CAG in addition to telomerase activation , provide the theoretical basis for anti-aging drugs.