美國(guó)斯坦福大學(xué)的研究小組最近發(fā)現(xiàn),，去乙?；竤irtuin家族成員之一SIRT6可能對(duì)延緩衰老起關(guān)鍵作用，以前人們一直認(rèn)為,，只有其“親屬”SIRT1才與衰老有關(guān),。研究人員還首次證明sirtuin能調(diào)控基因活動(dòng)。該研究發(fā)表在最新一期的《細(xì)胞》雜志上,。
研究小組發(fā)現(xiàn),，失去SIRT6的老鼠剛開(kāi)始幾周內(nèi)能正常生長(zhǎng)，但之后會(huì)很快衰老,，并在幾個(gè)月后死于低血糖,。
該研究小組曾在去年證明SIRT6是一種酶，能夠從組蛋白的一個(gè)特定點(diǎn)上移走名為乙?；M的化學(xué)物質(zhì),。組蛋白對(duì)調(diào)控基因表達(dá)非常重要，而從組蛋白中移除乙?；M就會(huì)“關(guān)閉”某些基因表達(dá),。
研究小組還發(fā)現(xiàn)，SIRT6同一個(gè)久負(fù)盛名的蛋白NF-kappaB（NF-kB）一起,，可以支配同衰老,、炎癥和新陳代謝相關(guān)基因的活動(dòng)。當(dāng)失去SIRT6時(shí),，NF-kappaB變得過(guò)度活躍,，開(kāi)啟同衰老相關(guān)的基因。而當(dāng)減少NF-kappaB數(shù)量后,，老鼠會(huì)恢復(fù)到正常的生命長(zhǎng)度,，許多早熟的老化癥狀也會(huì)消失，但老鼠的血糖仍很低,，許多其他沒(méi)有被NF-kappaB調(diào)節(jié)的基因也會(huì)出現(xiàn)反?；顒?dòng)。
研究人員希望能開(kāi)發(fā)出與SIRT6有關(guān)的藥物,，用來(lái)治療如骨質(zhì)疏松癥等同衰老相關(guān)的疾病,，并繼續(xù)研究SIRT6的濃度和衰老等活動(dòng)變化關(guān)系的規(guī)律,。（生物谷Bioon.com）
生物谷推薦原始出處：
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.
