衰老是人和动物都无法避免的生理过程，真核细胞在衰老的过程中基因组会变得失去稳定性，基因表达也会基因组的不稳定性而发生改变。研究发现，酵母细胞中的组蛋白脱乙酰基酶Sir2具有沉默转录子和稳定重复DNA的功效，但是，当细胞开始老化或是DNA断裂情况发生的时候，Sir复合物会失去原来的功能，变得不具有沉默基因的能力，并最终导致酵母失去自我增殖的能力，这是酵母老化过程中伴随发生的典型特征。
为了解哺乳动物是否具有相似的情况，研究者用小鼠胚胎干细胞来进行试验，结果发现SIRT1的功能与酵母的Sir2相似，SIRT1具有抑制重复DNA片段各种基因表达的功能。当DNA发生断裂的情况时，SIRT1就会从基因组转座子上掉落，并重新定位促进DNA修复，改变转录过程，这一情况在老化的细胞中同样会出现。如果增加SIRT1的表达量可有效保护基因组稳定性遭破坏的细胞维持活性，抑制老化带来的基因组转录变化。
所以说，DNA造到破坏可诱导SIRT1重新分配，并随之改变基因组的转录情况，改变蛋白的表达情况，这一机制可能是真核细胞在老化过程中一个保守的机制。（生物谷Bioon.com）
生物谷推荐原始出处：
Cell, Volume 135, Issue 5, 907-918, 28 November 2008 doi:10.1016/j.cell.2008.10.025
SIRT1 Redistribution on Chromatin Promotes Genomic Stability but Alters Gene Expression during Aging
Philipp Oberdoerffer1,Shaday Michan1,Michael McVay1,Raul Mostoslavsky2,James Vann3,Sang-Kyu Park3,Andrea Hartlerode4,Judith Stegmuller1,7,Angela Hafner1,Patrick Loerch1,Sarah M. Wright5,Kevin D. Mills5,Azad Bonni1,Bruce A. Yankner1,Ralph Scully4,Tomas A. Prolla3,Frederick W. Alt6andDavid A. Sinclair1,,
1 Department of Pathology and Glenn Labs for Aging Research, Harvard Medical School, Boston, MA 02115, USA
2 Massachusetts General Hospital Cancer Center, Boston, MA 02114, USA
3 University of Wisconsin, Department of Genetics and Medical Genetics, Madison, WI 53706, USA
4 Department of Medicine, Harvard Medical School and Beth Israel Deaconess Medical Center, Boston, MA 02115, USA
5 The Jackson Laboratory, Bar Harbor, ME 04609, USA
6 Howard Hughes Medical Institute, The Children's Hospital, Immune Disease Institute, and Department of Genetics, Harvard Medical School, Boston, MA 02115, USA
7 Present address: Max Planck Institute for Experimental Medicine, 37075 G?ttingen, Germany
Genomic instability and alterations in gene expression are hallmarks of eukaryotic aging. The yeast histone deacetylase Sir2 silences transcription and stabilizes repetitive DNA, but during aging or in response to a DNA break, the Sir complex relocalizes to sites of genomic instability, resulting in the desilencing of genes that cause sterility, a characteristic of yeast aging. Using embryonic stem cells, we show that mammalian Sir2, SIRT1, represses repetitive DNA and a functionally diverse set of genes across the mouse genome. In response to DNA damage, SIRT1 dissociates from these loci and relocalizes to DNA breaks to promote repair, resulting in transcriptional changes that parallel those in the aging mouse brain. Increased SIRT1 expression promotes survival in a mouse model of genomic instability and suppresses age-dependent transcriptional changes. Thus, DNA damage-induced redistribution of SIRT1 and other chromatin-modifying proteins may be a conserved mechanism of aging in eukaryotes.
