雌激素上调SIRT1抗衰老机制研究进展

Research Progress of Estrogen Upregulation of SIRT1 Activity in Anti-aging

沉默信息调节因子2(silent information regulator 2,Sir2)及其蛋白家族,是一种高度保守的依赖于烟酰胺腺嘌呤二核苷酸(NAD+)的去乙酰化酶,最先在酵母中发现。哺乳动物中Sir2相关酶1(SIRT1)与其同源性最高,被认为是长寿蛋白,通过能量限制来发挥抗衰老作用。在多种组织器官中SIRT1通过与组蛋白或非组蛋白的相互作用调控多种生理过程,如调节能量代谢、脂质氧化及延缓心脑血管疾病等老年疾病的发生发展,进而延缓衰老。既往研究表明雌激素在抗衰老方面发挥重要作用,传统观点认为雌激素通过直接或间接地与雌激素受体结合激活目的基因而发挥抗衰老作用。而近期研究表明雌激素可以通过多条旁路途径上调SIRT1的表达而延缓细胞衰老。综述雌激素上调SIRT1的表达途径以探讨雌激素抗衰老机制。

The silent information regulator 2 （Sir2） and family proteins are highly conserved NAD＋（nieotinamide adenine dinucleotide）-dependent deacetylases, and were originally discovered in yeast. SIRT1 is the highest homology with Sir2 in mammal, is considered to be long-lived protein limited by energy to give play to the role of anti-aging. SIRT1 regulates physiological processes through histones and non-histone proteins to extend life span, such as adjusting the energy metabolism, lipid oxidation and delay the onset of old age diseases such as cardiovascular development, and anti-aging. Studies have shown that estrogen plays a vital role in anti-aging. Conventional viewpoints suggested that estrogen combined with the estrogen receptor （ER） in directly or indirectly to activate the target genes in anti-aging. However, recent research shows that estrogen upregulated SIRTI by multiple pathways and delayed cell senescence. This paper discuss the anti-aging mechanism of estrogen by summarizing the exoression pathways of estrozen uo-regulating SIRT1.