Integrin-linked kinase modulates longevity and thermotolerance in C. elegans through neuronal control of HSF-1.
Integrin-linked kinase modulates longevity and thermotolerance in C. elegans through neuronal control of HSF-1.
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DOI：
10.1111/acel.12189
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发表时间：
2014-06
期刊：
影响因子：
7.8
通讯作者：
Hansen M
中科院分区：
文献类型：
--
作者：
Kumsta C;Ching TT;Nishimura M;Davis AE;Gelino S;Catan HH;Yu X;Chu CC;Ong B;Panowski SH;Baird N;Bodmer R;Hsu AL;Hansen M
整合素信号复合体在许多物种的细胞骨架组织和细胞黏附中发挥重要作用。在秀丽线虫和黑腹果蝇中，整合素信号复合体的组成部分都与衰老有关，但其潜在功能的机制尚不清楚。在这里，我们研究了整合素连接的激酶(ILK)，整合素信号复合体的关键成分，在决定寿命中的作用。我们报告了线虫和果蝇中ilk基因的减少增加了对热应激的抵抗力，并导致线虫的寿命延长，而不主要影响细胞骨架的完整性。在线虫中，ILK耗竭诱导的寿命和耐热性是由热休克因子-1(HSF-1)介导的，热休克因子-1是热休克反应(HSR)的主要转录调节因子。ILK水平的降低增加了HSF-1的转录和激活，并导致了在HSR中起作用的基因子集的表达增强。此外，由于ILK的减少而导致的HSR相关基因、寿命和耐热性的诱导需要热敏神经元AFD和中间神经元AIY，它们在典型的HSR中起着关键作用。值得注意的是，ILK在邻近的神经元中表达，但在AFD或AIY中不表达，这意味着ILK的减少通过热敏神经元启动了细胞非自治信号，从而引发了非规范的HSR。因此，我们的结果确定HSF-1是一种新的生物体对ILK水平降低的反应的效应器，并表明ILK抑制以一种细胞非自主的方式调节HSF-1，以提高线虫的抗逆性和寿命。
Integrin-signaling complexes play important roles in cytoskeletal organization and cell adhesion in many species. Components of the integrin-signaling complex have been linked to aging in both Caenorhabditis elegans and Drosophila melanogaster, but the mechanism underlying this function is unknown. Here, we investigated the role of integrin-linked kinase (ILK), a key component of the integrin-signaling complex, in lifespan determination. We report that genetic reduction of ILK in both C. elegans and Drosophila increased resistance to heat stress, and led to lifespan extension in C. elegans without majorly affecting cytoskeletal integrity. In C. elegans, longevity and thermotolerance induced by ILK depletion was mediated by heat-shock factor-1 (HSF-1), a major transcriptional regulator of the heat-shock response (HSR). Reduction in ILK levels increased hsf-1 transcription and activation, and led to enhanced expression of a subset of genes with roles in the HSR. Moreover, induction of HSR-related genes, longevity and thermotolerance caused by ILK reduction required the thermosensory neurons AFD and interneurons AIY, which are known to play a critical role in the canonical HSR. Notably, ILK was expressed in neighboring neurons, but not in AFD or AIY, implying that ILK reduction initiates cell nonautonomous signaling through thermosensory neurons to elicit a noncanonical HSR. Our results thus identify HSF-1 as a novel effector of the organismal response to reduced ILK levels and show that ILK inhibition regulates HSF-1 in a cell nonautonomous fashion to enhance stress resistance and lifespan in C. elegans.
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影响因子：
7.8
作者：
Jensen, Louise T.;Moller, Tine H.;Olsen, Anders
通讯作者：
Olsen, Anders
影响因子：
4.5
作者：
Hansen M;Hsu AL;Dillin A;Kenyon C
通讯作者：
Kenyon C
DOI：
10.1093/gerona/glr225
发表时间：
2012-07-01
影响因子：
5.1
作者：
Mendenhall, Alexander R.;Tedesco, Patricia M.;Johnson, Thomas E.
通讯作者：
Johnson, Thomas E.
影响因子：
64.8
作者：
Lange, Anika;Wickstroem, Sara A.;Faessler, Reinhard
通讯作者：
Faessler, Reinhard
化学感应和热感应系统对寿命的调节：无脊椎动物的发现及其在哺乳动物衰老中的影响。
影响因子：
3.7
作者：
Jeong DE;Artan M;Seo K;Lee SJ
通讯作者：
Lee SJ