Pickering Andrew M, Lehr Marcus, Gendron Christi M, Pletcher Scott D, Miller Richard A
Barshop Institute for Longevity and Aging Studies, University of Texas Health Science Center at San Antonio, San Antonio, TX, USA.
Department of Pathology, University of Michigan, Ann Arbor, MI, USA.
Aging Cell. 2017 Aug;16(4):683-692. doi: 10.1111/acel.12596. Epub 2017 May 5.
In a survey of enzymes related to protein oxidation and cellular redox state, we found activity of the redox enzyme thioredoxin reductase (TXNRD) to be elevated in cells from long-lived species of rodents, primates, and birds. Elevated TXNRD activity in long-lived species reflected increases in the mitochondrial form, TXNRD2, rather than the cytosolic forms TXNRD1 and TXNRD3. Analysis of published RNA-Seq data showed elevated TXNRD2 mRNA in multiple organs of longer-lived primates, suggesting that the phenomenon is not limited to skin-derived fibroblasts. Elevation of TXNRD2 activity and protein levels was also noted in liver of three different long-lived mutant mice, and in normal male mice treated with a drug that extends lifespan in males. Overexpression of mitochondrial TXNRD2 in Drosophila melanogaster extended median (but not maximum) lifespan in female flies with a small lifespan extension in males; in contrast, overexpression of the cytosolic form, TXNRD1, did not produce a lifespan extension.
在一项关于与蛋白质氧化和细胞氧化还原状态相关酶的调查中，我们发现氧化还原酶硫氧还蛋白还原酶（TXNRD）的活性在啮齿动物、灵长类动物和鸟类的长寿物种细胞中有所升高。长寿物种中TXNRD活性的升高反映了线粒体形式TXNRD2的增加，而非胞质形式TXNRD1和TXNRD3。对已发表的RNA测序数据的分析表明，在寿命较长的灵长类动物的多个器官中TXNRD2 mRNA水平升高，这表明该现象不限于皮肤来源的成纤维细胞。在三种不同的长寿突变小鼠的肝脏中，以及在用延长雄性寿命的药物处理的正常雄性小鼠中，也观察到TXNRD2活性和蛋白质水平的升高。在果蝇中过表达线粒体TXNRD2可延长雌性果蝇的中位（而非最大）寿命，雄性果蝇的寿命也有小幅延长；相比之下，过表达胞质形式的TXNRD1则不会延长寿命。
