A proteomic atlas of insulin signalling reveals tissue-specific mechanisms of longevity assurance.
A proteomic atlas of insulin signalling reveals tissue-specific mechanisms of longevity assurance.
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DOI：
10.15252/msb.20177663
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发表时间：
2017-09-15
影响因子：
9.9
通讯作者：
Partridge L
中科院分区：
文献类型：
--
作者：
Tain LS;Sehlke R;Jain C;Chokkalingam M;Nagaraj N;Essers P;Rassner M;Grönke S;Froelich J;Dieterich C;Mann M;Alic N;Beyer A;Partridge L
降低胰岛素/IGF信号（IIS）网络的活性可以改善实验室动物和人类衰老的影响。尽管在长寿IIS突变体中的转录组重构已被广泛记录，但导致寿命延长的因果机制，特别是在特定组织中，仍不清楚。我们已经表征了长寿果蝇IIS突变体和对照中四个关键胰岛素敏感组织的蛋白质组，并检测到44%的预测蛋白质组（6，085种蛋白质）。在突变体中，脂肪体中核糖体相关蛋白的表达减少，相应的组织特异性翻译减少。线粒体电子传递链蛋白在脂肪体中的表达增加，导致呼吸增加，这是IIS介导的寿命延长所必需的，并且单独足以介导它。蛋白酶体亚基在IIS突变体肠道中显示出改变的表达，并且肠道特异性RPN 6蛋白酶体亚基的过表达足以增加蛋白酶体活性并延长寿命，而蛋白酶体活性的抑制则消除了IIS介导的寿命。因此，我们的研究揭示了细胞过程对降低IIS的显著组织特异性反应，这些反应共同作用以改善衰老。
Lowered activity of the insulin/IGF signalling (IIS) network can ameliorate the effects of ageing in laboratory animals and, possibly, humans. Although transcriptome remodelling in long‐lived IIS mutants has been extensively documented, the causal mechanisms contributing to extended lifespan, particularly in specific tissues, remain unclear. We have characterized the proteomes of four key insulin‐sensitive tissues in a long‐lived Drosophila IIS mutant and control, and detected 44% of the predicted proteome (6,085 proteins). Expression of ribosome‐associated proteins in the fat body was reduced in the mutant, with a corresponding, tissue‐specific reduction in translation. Expression of mitochondrial electron transport chain proteins in fat body was increased, leading to increased respiration, which was necessary for IIS‐mediated lifespan extension, and alone sufficient to mediate it. Proteasomal subunits showed altered expression in IIS mutant gut, and gut‐specific over‐expression of the RPN6 proteasomal subunit, was sufficient to increase proteasomal activity and extend lifespan, whilst inhibition of proteasome activity abolished IIS‐mediated longevity. Our study thus uncovered strikingly tissue‐specific responses of cellular processes to lowered IIS acting in concert to ameliorate ageing.
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影响因子：
7.8
作者：
Bai H;Kang P;Tatar M
通讯作者：
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影响因子：
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作者：
Cox, Juergen;Neuhauser, Nadin;Mann, Matthias
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DOI：
10.1093/gerona/61.7.675
发表时间：
2006-07-01
影响因子：
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影响因子：
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作者：
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通讯作者：
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影响因子：
14.9
作者：
Bailey TL;Boden M;Buske FA;Frith M;Grant CE;Clementi L;Ren J;Li WW;Noble WS
通讯作者：
Noble WS