Co-chaperone p23 regulates C. elegans Lifespan in Response to Temperature.
Co-chaperone p23 regulates C. elegans Lifespan in Response to Temperature.
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DOI：
10.1371/journal.pgen.1005023
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发表时间：
2015-04
期刊：
影响因子：
4.5
通讯作者：
Antebi A
中科院分区：
文献类型：
--
作者：
Horikawa M;Sural S;Hsu AL;Antebi A
温度有效地调节各种生理过程，包括生物体运动、生长速率、繁殖和衰老。在外温动物中，寿命与温度成反比，温度越高，动物寿命越短。对寿命和其他过程的热效应归因于代谢率的被动变化，但最近的证据也表明了一个受调节的过程。在这里，我们证明，响应于温度，daf-41/ZC 395.10，C. p23共伴侣蛋白/前列腺素E合酶-3的elegans同源物，控制进入长寿的dauer滞育并调节成虫寿命。daf-41缺失触发在升高的温度下依赖于神经感觉机制（daf-10/IFT 122）、胰岛素/IGF-1信号传导（daf-16/FOXO）和类固醇信号传导（daf-12/FXR）组成性进入道尔滞育。令人惊讶的是，daf-41突变改变了对温度的长寿反应，在25°C下比野生型寿命长，但在15°C下比野生型寿命短。在25°C下，长寿表型通过daf-16/FOXO和热休克因子hsf-1起作用，而短命表型集中在daf-16/FOXO上，并依赖于daf-12/FXR类固醇受体。相关的daf-41影响的表达的ESTA-16和HSF-1的靶基因在高温下，和daf-41动物的核提取物显示出增加占用的热休克反应元件。我们的研究表明，daf-41/p23调节长寿途径中的关键转录变化，以响应温度。温度是影响冷血动物和温血动物衰老的关键环境因素。在无脊椎动物中，寿命与温度成反比，温度越高，发育越快，但寿命越短。这种现象通常归因于代谢率的被动变化，但最近的研究表明，这一过程是受调节的。在这项研究中，我们确定了共伴侣蛋白p23在线虫C。elegans作为一个重要的调制器寿命在响应温度。辅分子伴侣与客户蛋白结合以帮助其折叠或稳定其形状，从而调节其活性。值得注意的是，相对于正常野生型动物，p23的缺失导致动物在高温下寿命长，在低温下寿命短。我们的实验表明，p23通过神经感觉装置调节寿命。这些反过来又影响了介导胰岛素/IGF转录输出、热休克反应和类固醇信号传导的关键长寿调节因子。这些研究表明，由p23形成的复合物在调节寿命对温度的反应中起着核心作用。
Temperature potently modulates various physiologic processes including organismal motility, growth rate, reproduction, and ageing. In ectotherms, longevity varies inversely with temperature, with animals living shorter at higher temperatures. Thermal effects on lifespan and other processes are ascribed to passive changes in metabolic rate, but recent evidence also suggests a regulated process. Here, we demonstrate that in response to temperature, daf-41/ZC395.10, the C. elegans homolog of p23 co-chaperone/prostaglandin E synthase-3, governs entry into the long-lived dauer diapause and regulates adult lifespan. daf-41 deletion triggers constitutive entry into the dauer diapause at elevated temperature dependent on neurosensory machinery (daf-10/IFT122), insulin/IGF-1 signaling (daf-16/FOXO), and steroidal signaling (daf-12/FXR). Surprisingly, daf-41 mutation alters the longevity response to temperature, living longer than wild-type at 25°C but shorter than wild-type at 15°C. Longevity phenotypes at 25°C work through daf-16/FOXO and heat shock factor hsf-1, while short lived phenotypes converge on daf-16/FOXO and depend on the daf-12/FXR steroid receptor. Correlatively daf-41 affected expression of DAF-16 and HSF-1 target genes at high temperature, and nuclear extracts from daf-41 animals showed increased occupancy of the heat shock response element. Our studies suggest that daf-41/p23 modulates key transcriptional changes in longevity pathways in response to temperature. Temperature is a critical environmental factor that affects ageing in both cold-blooded and warm-blooded species. In invertebrate animals, lifespan varies inversely with temperature, with higher temperature resulting in faster development but shorter lifespan. This phenomenon has been usually attributed to passive changes in metabolic rate, but recent work suggests that this process is regulated. In this study, we identify the co-chaperone protein p23 in the nematode C. elegans as an important modulator of longevity in response to temperature. Co-chaperones bind to client proteins to assist in their folding or stabilize their shape, thereby regulating their activity. Remarkably, deletion of p23 results in animals that are long lived at high temperatures and short lived at low temperatures relative to normal wild type animals. Our experiments indicate that p23 regulates lifespan through the neurosensory apparatus. These in turn impinge on key longevity regulators that mediate the transcriptional outputs of insulin/IGF, heat shock response and steroidal signaling. These studies suggest that complexes formed by p23 play a central role in regulating longevity in response to temperature.
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影响因子：
11.8
作者：
Gerisch, B;Weitzel, C;Antebi, A
通讯作者：
Antebi, A
影响因子：
4.6
作者：
da Graca, LS;Zimmerman, KK;Patterson, GI
通讯作者：
Patterson, GI
影响因子：
56.9
作者：
Conti, Bruno;Sanchez-Alavez, Manuel;Bartfai, Tamas
通讯作者：
Bartfai, Tamas
DOI：
10.1093/gerona/gls086
发表时间：
2012-06-01
影响因子：
5.1
作者：
Brown-Borg, Holly M.;Bartke, Andrzej
通讯作者：
Bartke, Andrzej
影响因子：
4.8
作者：
Honda, Y;Honda, S
通讯作者：
Honda, S