Horikawa Makoto, Sural Surojit, Hsu Ao-Lin, Antebi Adam
Max Planck Institute for Biology of Ageing, Cologne, Germany.
University of Michigan, Department of Internal Medicine, Division of Geriatric and Palliative Medicine, Ann Arbor, Michigan, United States of America; University of Michigan, Department of Molecular and Integrative Physiology, Ann Arbor, Michigan, United States of America.
PLoS Genet. 2015 Apr 1;11(4):e1005023. doi: 10.1371/journal.pgen.1005023. eCollection 2015 Apr.
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.
温度能强有力地调节各种生理过程，包括机体运动、生长速率、繁殖和衰老。在变温动物中，寿命与温度呈负相关，动物在较高温度下寿命较短。热对寿命和其他过程的影响归因于代谢率的被动变化，但最近的证据也表明存在一个受调控的过程。在这里，我们证明，秀丽隐杆线虫中与p23共伴侣蛋白/前列腺素E合酶-3同源的daf-41/ZC395.10，在响应温度时，控制进入长寿的滞育期并调节成虫寿命。daf-41缺失会在高温下触发依赖神经感觉机制（daf-10/IFT122）、胰岛素/胰岛素样生长因子-1信号通路（daf-16/FOXO）和类固醇信号通路（daf-12/FXR）的组成型滞育期进入。令人惊讶的是，daf-41突变改变了对温度的寿命反应，在25°C时比野生型寿命长，但在15°C时比野生型寿命短。25°C时的寿命表型通过daf-16/FOXO和热休克因子hsf-1起作用，而短寿命表型则集中在daf-16/FOXO上，并依赖于daf-12/FXR类固醇受体。相应地，daf-41在高温下影响DAF-16和HSF-1靶基因的表达，来自daf-41动物的核提取物显示热休克反应元件的占有率增加。我们的研究表明，daf-41/p23响应温度调节长寿途径中的关键转录变化。
