摘要
在酵母、线虫和果蝇中,Sir2基因家族是寿命调节的关键因子。哺乳动物的Sirt基因家族在进化上与Sir2基因高度同源,共有7个成员。Sir2基因调节酵母寿命的机理已比较清楚。而哺乳动物Sirt基因,特别是Sirt1基因与细胞衰老的关系正在成为新的研究热点。最近的研究表明,在热量限制或氧化逆境条件下,SIRT1蛋白主要是通过以下3个途径影响细胞寿命:一是SIRT1蛋白抑制PPAR-γ减少细胞的脂质过氧化的损伤;二是SIRT1蛋白通过调控p53的活性影响细胞寿命;三是SIRT1蛋白通过调控FOXO的信号通路,启动细胞的抗氧化途径。进一步研究Sirt基因家族对揭示哺乳动物寿命之谜具有重要的科学意义。
The Sir2 gene family can modulate cell lifespan in Saccharomyces cerevisiae, Caenorhabditis elegans, and Drosophila. The Sir2 homologues in mammalian is called Sift gene family and it comprises seven members. The mechanism of lifespan regulation by Sir2 gene in the Saccharomyces cerevisiae is relatively clear. While, the role of Sift genes, especially, the Sirtl gene, in protection mammalian cell from senescence become a hot spot of research interest. Current knowledge shows that SIRT1 participates in three pathways to regulate lifespan during caloric restriction and oxidative stress. First, SIRT1 represses PPAR-γ to induce a shedding of body fat from white adipose tissue in order to reduce the toxic effects of LPA; Second, SIRT1 expression can influence p53 function via two distinct mechanism, which have opposite effect on net p53 activity; Third, SIRT1 increases the ability of FOXO to resistent oxidative stress. In this review, the latest findings regarding SIRT gene family and their role in regulation of mammalian lifespan were summarized and discussed.
出处
《生物物理学报》
CAS
CSCD
北大核心
2006年第1期7-11,共5页
Acta Biophysica Sinica
基金
国家自然科学基金项目(30270501
30130100)~~
