Lifespan extension by increased expression of the Drosophila homologue of the IGFBP7 tumour suppressor.
Lifespan extension by increased expression of the Drosophila homologue of the IGFBP7 tumour suppressor.
复制标题
DOI：
10.1111/j.1474-9726.2010.00653.x
复制
发表时间：
2011-02
期刊：
影响因子：
7.8
通讯作者：
Partridge L
中科院分区：
文献类型：
--
作者：
Alic N;Hoddinott MP;Vinti G;Partridge L
哺乳动物具有多种胰岛素样生长因子（IGF）结合蛋白（IGFBP）和相关蛋白，可调节胰岛素/IGF信号传导（IIS）的活性，IIS是一种影响动物寿命的保守神经内分泌信号传导途径。在这里，我们研究了IGFBP样蛋白水平的增加是否可以延长寿命，使用果蝇作为模式生物。我们证明，Imaginal形态发生蛋白-晚2（IMP-L2），一种分泌的蛋白质和苍蝇同源的人IGFBP 7肿瘤抑制因子，能够结合至少两个7果蝇胰岛素样肽（DILP），即天然DILP 2和DILP 5中存在的成年苍蝇。Imp-L2的表达增加导致与IIS下调一致的成体表型变化，包括eIF-4 E结合蛋白mRNA的积累、储存脂质的增加、繁殖力降低和氧化应激抗性增强。增加的Imp-L2导致dilp 2、dilp 3和dilp 5 mRNA的上调，揭示了通过蝇肠和/或脂肪体介导的反馈回路。重要的是，Imp-L2的过表达，普遍存在或限于DILP产生细胞或肠道和脂肪体，延长寿命。在成年发病诱导Imp-L2后也可以观察到这种延长的寿命，表明其不归因于发育变化。我们的研究结果指出，IGFBP或相关蛋白质，如IGFBP 7，在哺乳动物衰老中发挥作用的可能性。
Mammals possess multiple insulin-like growth factor (IGF) binding proteins (IGFBPs), and related proteins, that modulate the activity of insulin/IGF signalling (IIS), a conserved neuroendocrine signalling pathway that affects animal lifespan. Here, we examine if increased levels of an IGFBP-like protein can extend lifespan, using Drosophila as the model organism. We demonstrate that Imaginal morphogenesis protein-Late 2 (IMP-L2), a secreted protein and the fly homologue of the human IGFBP7 tumour suppressor, is capable of binding at least two of the seven Drosophila insulin-like peptides (DILPs), namely native DILP2 and DILP5 as present in the adult fly. Increased expression of Imp-L2 results in phenotypic changes in the adult consistent with down-regulation of IIS, including accumulation of eIF-4E binding protein mRNA, increase in storage lipids, reduced fecundity and enhanced oxidative stress resistance. Increased Imp-L2 results in up-regulation of dilp2, dilp3 and dilp5 mRNA, revealing a feedback circuit that is mediated via the fly gut and/or fat body. Importantly, over-expression of Imp-L2, ubiquitous or restricted to DILP-producing cells or gut and fat body, extends lifespan. This enhanced longevity can also be observed upon adult-onset induction of Imp-L2, indicating it is not attributable to developmental changes. Our findings point to the possibility that an IGFBP or a related protein, such as IGFBP7, plays a role in mammalian aging.
登录
查看更多内容
影响因子：
9.2
作者：
Brogiolo, W;Stocker, H;Hafen, E
通讯作者：
Hafen, E
影响因子：
10.5
作者：
LUO, LQ;LIAO, YJ;JAN, YN
通讯作者：
JAN, YN
影响因子：
7.8
作者：
Giannakou, Maria E.;Goss, Martin;Partridge, Linda
通讯作者：
Partridge, Linda
DOI：
10.1073/pnas.0405775102
发表时间：
2005-02-22
影响因子：
11.1
作者：
Broughton, SJ;Piper, MDW;Partridge, L
通讯作者：
Partridge, L
影响因子：
3.9
作者：
Ford, Daniel;Hoe, Nicholas;Tower, John
通讯作者：
Tower, John