Numerous theories of how and why aging occurs have been postulated but a definitive comprehensive explanation remains elusive. Attempts to unravel genetic details of aging resulted in the identification of a yeast gen...Numerous theories of how and why aging occurs have been postulated but a definitive comprehensive explanation remains elusive. Attempts to unravel genetic details of aging resulted in the identification of a yeast gene known as Sir2 as a modulator of life span. Identification and characterization of mammalian Sir2 homologs followed and has catapulted aging research to exciting new levels. This review begins with basic definitions of aging and then describes some of the most common theories of the aging process. The review presents information related to the initial discovery of the Sirtuins and summarizes some of the recent advances in defining roles for Sirtuin family members. SIRT6 is discussed in greater detail because it is one of the best characterized of the mammalian Sirtuins and seems to be one of the most important in the aging process and metabolic regulation.展开更多
主要定位于线粒体的沉默信息调节因子3(silent information regulators 3,SIRT3)是一种具有调节线粒体蛋白功能、维持细胞抗氧化状态的烟酰胺腺嘌呤二核苷酸依赖性蛋白去乙酰化酶。研究发现,SIRT3与多种神经退行性疾病关系密切。神经退...主要定位于线粒体的沉默信息调节因子3(silent information regulators 3,SIRT3)是一种具有调节线粒体蛋白功能、维持细胞抗氧化状态的烟酰胺腺嘌呤二核苷酸依赖性蛋白去乙酰化酶。研究发现,SIRT3与多种神经退行性疾病关系密切。神经退行性疾病是一种进行性的且不可逆转的神经系统疾病,目前其病因尚不明确,但有大量证据表明氧化应激和线粒体功能障碍参与了其发生发展。SIRT3通过去乙酰化调节多种参与线粒体能量代谢的酶和抗氧化防御蛋白的活性及生物学功能,进而影响神经退行性疾病的进程。本文综述了SIRT3在调节线粒体呼吸链和抗氧化系统的功能特点、在神经保护中发挥的作用,及其与多种神经退行性疾病之间的关系,以期为SIRT3作为神经退行性疾病治疗的靶点提供新策略。展开更多
文摘Numerous theories of how and why aging occurs have been postulated but a definitive comprehensive explanation remains elusive. Attempts to unravel genetic details of aging resulted in the identification of a yeast gene known as Sir2 as a modulator of life span. Identification and characterization of mammalian Sir2 homologs followed and has catapulted aging research to exciting new levels. This review begins with basic definitions of aging and then describes some of the most common theories of the aging process. The review presents information related to the initial discovery of the Sirtuins and summarizes some of the recent advances in defining roles for Sirtuin family members. SIRT6 is discussed in greater detail because it is one of the best characterized of the mammalian Sirtuins and seems to be one of the most important in the aging process and metabolic regulation.
文摘目的:探讨益气养阴通络方(Yiqi Yangyin Tongluo Formula,YYT)对糖尿病肾病(Diabetic Nephropathy,DN)db/db小鼠可能的肾脏保护机制。方法:24只db/db小鼠随机分为模型组、厄贝沙坦组(19.5 mg/kg)和YYT组(37.44 g/kg),正常组为8只db/m小鼠,模型组与正常组给予等体积蒸馏水灌胃,厄贝沙坦组和YYT组给予对应药物灌胃,连续干预8周。检测各组小鼠24 h尿蛋白(24 h UTP)、空腹血糖(FBG)、血清尿素氮(BUN)、肌酐(Scr)含量;苏木精-伊红(HE)、过碘酸雪夫(PAS)染色和电镜观察肾脏病理变化;免疫组化法检测肾脏足细胞标志蛋白足细胞裂孔膜蛋白(Nephrin)、膜蛋白(Podocin)及自噬关键分子酵母Atg6同系物1(Beclin1)、自噬底物P62表达水平;Western blot检测小鼠肾脏AMP依赖蛋白激酶(AMPK)、磷酸化AMP依赖蛋白激酶(p-AMPK)、沉默信息调节因子1(SIRT1)蛋白表达。结果:与正常组相比,模型组小鼠24 h UTP、FBG、BUN、Scr均升高(P<0.05);肾脏组织出现明显病理改变;肾组织Nephrin、Podocin、Beclin1蛋白表达降低(P<0.05),P62表达升高(P<0.05);通路蛋白p-AMPK/AMPK、SIRT1表达降低(P<0.05)。与模型组相比,厄贝沙坦组和YYT组小鼠24 h UTP、FBG、BUN、Scr降低(P<0.05);肾脏病理损伤出现不同程度减轻;肾组织Nephrin、Podocin、Beclin1蛋白表达升高(P<0.05),P62表达降低(P<0.05);通路蛋白p-AMPK/AMPK、SIRT1表达升高(P<0.05)。YYT组与厄贝沙坦组相比,差异无统计学意义(P>0.05)。结论:YYT可增强自噬,减轻足细胞损伤,延缓疾病进展,其作用机制可能与激活AMPK/SIRT1信号通路相关。
文摘主要定位于线粒体的沉默信息调节因子3(silent information regulators 3,SIRT3)是一种具有调节线粒体蛋白功能、维持细胞抗氧化状态的烟酰胺腺嘌呤二核苷酸依赖性蛋白去乙酰化酶。研究发现,SIRT3与多种神经退行性疾病关系密切。神经退行性疾病是一种进行性的且不可逆转的神经系统疾病,目前其病因尚不明确,但有大量证据表明氧化应激和线粒体功能障碍参与了其发生发展。SIRT3通过去乙酰化调节多种参与线粒体能量代谢的酶和抗氧化防御蛋白的活性及生物学功能,进而影响神经退行性疾病的进程。本文综述了SIRT3在调节线粒体呼吸链和抗氧化系统的功能特点、在神经保护中发挥的作用,及其与多种神经退行性疾病之间的关系,以期为SIRT3作为神经退行性疾病治疗的靶点提供新策略。
