Braidy Nady, Poljak Anne, Grant Ross, Jayasena Tharusha, Mansour Hussein, Chan-Ling Tailoi, Smythe George, Sachdev Perminder, Guillemin Gilles J
Centre for Healthy Brain Ageing, School of Psychiatry, University of New South Wales Sydney, NSW, Australia.
Faculty of Medicine, School of Medical Sciences, University of New South Wales Sydney, NSW, Australia ; Bioanalytical Mass Spectrometry Facility, University of New South Wales Sydney, NSW, Australia.
Front Cell Neurosci. 2015 May 8;9:167. doi: 10.3389/fncel.2015.00167. eCollection 2015.
Although there are seven mammalian sirtuins (SIRT1-7), little is known about their expression in the aging brain. To characterize the change(s) in mRNA and protein expression of SIRT1-7 and their associated proteins in the brain of "physiologically" aged Wistar rats. We tested mRNA and protein expression levels of rat SIRT1-7, and the levels of associated proteins in the brain using RT-PCR and western blotting. Our data shows that SIRT1 expression increases with age, concurrently with increased acetylated p53 levels in all brain regions investigated. SIRT2 and FOXO3a protein levels increased only in the occipital lobe. SIRT3-5 expression declined significantly in the hippocampus and frontal lobe, associated with increases in superoxide and fatty acid oxidation levels, and acetylated CPS-1 protein expression, and a reduction in MnSOD level. While SIRT6 expression declines significantly with age acetylated H3K9 protein expression is increased throughout the brain. SIRT7 and Pol I protein expression increased in the frontal lobe. This study identifies previously unknown roles for sirtuins in regulating cellular homeostasis and healthy aging.
尽管存在七种哺乳动物沉默调节蛋白（SIRT1 - 7），但我们对它们在衰老大脑中的表达了解甚少。为了表征“生理”衰老的Wistar大鼠大脑中SIRT1 - 7及其相关蛋白的mRNA和蛋白质表达变化。我们使用逆转录聚合酶链反应（RT-PCR）和蛋白质免疫印迹法检测了大鼠SIRT1 - 7的mRNA和蛋白质表达水平，以及大脑中相关蛋白的水平。我们的数据表明，SIRT1的表达随年龄增长而增加，同时在所研究的所有脑区中乙酰化p53水平也增加。SIRT2和FOXO3a蛋白水平仅在枕叶中增加。SIRT3 - 5在海马体和额叶中的表达显著下降，这与超氧化物和脂肪酸氧化水平的增加、乙酰化CPS - 1蛋白表达的增加以及MnSOD水平的降低有关。虽然SIRT6的表达随年龄显著下降，但乙酰化H3K9蛋白表达在整个大脑中增加。SIRT7和Pol I蛋白表达在额叶中增加。这项研究确定了沉默调节蛋白在调节细胞内稳态和健康衰老方面以前未知的作用。
