美国斯坦福大学的研究小组最近发现，去乙酰化酶sirtuin家族成员之一SIRT6可能对延缓衰老起关键作用，以前人们一直认为，只有其“亲属”SIRT1才与衰老有关。研究人员还首次证明sirtuin能调控基因活动。该研究发表在最新一期的《细胞》杂志上。

研究小组发现，失去SIRT6的老鼠刚开始几周内能正常生长，但之后会很快衰老，并在几个月后死于低血糖。

该研究小组曾在去年证明SIRT6是一种酶，能够从组蛋白的一个特定点上移走名为乙酰基组的化学物质。组蛋白对调控基因表达非常重要，而从组蛋白中移除乙酰基组就会“关闭”某些基因表达。

研究小组还发现，SIRT6同一个久负盛名的蛋白NF-kappaB（NF-kB）一起，可以支配同衰老、炎症和新陈代谢相关基因的活动。当失去SIRT6时，NF-kappaB变得过度活跃，开启同衰老相关的基因。而当减少NF-kappaB数量后，老鼠会恢复到正常的生命长度，许多早熟的老化症状也会消失，但老鼠的血糖仍很低，许多其他没有被NF-kappaB调节的基因也会出现反常活动。

研究人员希望能开发出与SIRT6有关的药物，用来治疗如骨质疏松症等同衰老相关的疾病，并继续研究SIRT6的浓度和衰老等活动变化关系的规律。

推荐原始出处：

Cell, Volume 136,9 January 2009 doi:10.1016/j.cell.2008.10.052

SIRT6 Links Histone H3 Lysine 9 Deacetylation to NF-κB-Dependent Gene Expression and Organismal Life Span

Tiara L.A. Kawahara1,2,5,Eriko Michishita3,4,5,Adam S. Adler1,2,5,Mara Damian3,4,5,Elisabeth Berber3,4,5,Meihong Lin1,Ron A. McCord2,3,4,Kristine C.L. Ongaigui1,Lisa D. Boxer3,4,Howard Y. Chang1,2,,andKatrin F. Chua2,3,4,,

1 Program in Epithelial Biology, Division of Endocrinology, Gerontology, and Metabolism, Stanford University School of Medicine, Stanford, CA 94305, USA
2 Cancer Biology Program, Division of Endocrinology, Gerontology, and Metabolism, Stanford University School of Medicine, Stanford, CA 94305, USA
3 Department of Medicine, Division of Endocrinology, Gerontology, and Metabolism, Stanford University School of Medicine, Stanford, CA 94305, USA
4 Geriatric Research, Education, and Clinical Center, VA Palo Alto Health Care System, Palo Alto, CA 94304, USA
5 These authors contributed equally to this work

Members of the sirtuin (SIRT) family of NAD-dependent deacetylases promote longevity in multiple organisms. Deficiency of mammalian SIRT6 leads to shortened life span and an aging-like phenotype in mice, but the underlying molecular mechanisms are unclear. Here we show that SIRT6 functions at chromatin to attenuate NF-κB signaling. SIRT6 interacts with the NF-κB RELA subunit and deacetylates histone H3 lysine 9 (H3K9) at NF-κB target gene promoters. In SIRT6-deficient cells, hyperacetylation of H3K9 at these target promoters is associated with increased RELA promoter occupancy and enhanced NF-κB-dependent modulation of gene expression, apoptosis, and cellular senescence. Computational genomics analyses revealed increased activity of NF-kB-driven gene expression programs in multiple Sirt6-deficient tissues invivo. Moreover, haploinsufficiency of RelA rescues the early lethality and degenerative syndrome of Sirt6-deficient mice. We propose that SIRT6 attenuates NF-κB signaling via H3K9 deacetylation at chromatin, and hyperactive NF-κB signaling may contribute to premature and normal aging.