欢迎您！东篱公司
退出
-
申报数据库
-
立项数据库
-
成果数据库
-
项目获奖数据库
中文摘要：
热量限制（caloric restriction,CR）可以引起细胞、生物体寿命延长和降低衰老相关疾病的发生,其中Sirtuin起着关键作用.Sirtuin将机体能量代谢和基因表达调控相偶联,通过赖氨酸去乙酰化改变蛋白质的活性和稳定性,从而调节衰老进程.酵母中度CR影响其复制寿命和时序寿命,主要依赖于激活Sir2,增加细胞内NAD＋/NADH的比例和调节尼克酰胺浓度来实现.类似的机制也存在于秀丽线虫和果蝇中.哺乳动物在CR条件下SIRT1蛋白表达应答性上升,细胞中NAM磷酸基转移酶能够直接影响NAM和NAD＋浓度,并影响SIRT1活性.NO表达增加能导致SIRT1上调和线粒体合成增加.SIRT1可能通过改变组蛋白、p53、NES1、FOXO等底物蛋白的乙酰化影响到细胞和个体的衰老.表明不同生物体中的Sirtuin及其同源类似物在CR条件下对衰老进程和寿命都起着非常重要的作用.
英文摘要：
Caloric restriction（CR） can delay aging and the onset of aging-related diseases. Sirtuin plays a key role in the aging process regulated by CR because of its ability to sense the metabolic status and to integrate into adaptive transcriptional outputs. Sirtuin regulates the aging process by altering protein activity and stability through lysine acetylation. Moderate CR in yeast influences replicative lifespan and chronological lifespan mainly by increasing the NAD＋/NADH ratio and regulating the level of nicotinamide. Similar mechanism also exist among Caenorhabditis elegans and Drosophila melanogasters. SIRT1 protein level increases in response to CR in mammals, leading to an increase in PNC1/Nampt expression, which favors the synthesis of NAD~ from NAM, potentially acting as a major mechanism to drop the leash of SIRT1 inhibition. NO up-regulates SIRT1 and mitochondrial biogenesis. Cellular and organism＇s senescence may be influenced through the deacetylation of histone, p53, NES1, FOXO by SIRT1, indicating sirtuin and its homologous analogues play important roles in aging process and lifespan extension under CR in different organisms.
同期刊论文项目
同项目期刊论文
Nar1 deficiency results in shortened lifespan and sensitivity to paraquat that is rescued by increas
Histone H4 lysine 16 hypoacetylation is associated with defective DNA repair and premature senescenc
期刊信息
位置：