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Translational Regulation of Non-autonomous Mitochondrial Stress Response Promotes Longevity.

Cell reports (2019-07-25)
Jianfeng Lan, Jarod A Rollins, Xiao Zang, Di Wu, Lina Zou, Zi Wang, Chang Ye, Zixing Wu, Pankaj Kapahi, Aric N Rogers, Di Chen
ABSTRACT

Reduced mRNA translation delays aging, but the underlying mechanisms remain underexplored. Mutations in both DAF-2 (IGF-1 receptor) and RSKS-1 (ribosomal S6 kinase/S6K) cause synergistic lifespan extension in C. elegans. To understand the roles of translational regulation in this process, we performed polysomal profiling and identified translationally regulated ribosomal and cytochrome c (CYC-2.1) genes as key mediators of longevity. cyc-2.1 knockdown significantly extends lifespan by activating the intestinal mitochondrial unfolded protein response (UPRmt), mitochondrial fission, and AMP-activated kinase (AMPK). The germline serves as the key tissue for cyc-2.1 to regulate lifespan, and germline-specific cyc-2.1 knockdown non-autonomously activates intestinal UPRmt and AMPK. Furthermore, the RNA-binding protein GLD-1-mediated translational repression of cyc-2.1 in the germline is important for the non-autonomous activation of UPRmt and synergistic longevity of the daf-2 rsks-1 mutant. Altogether, these results illustrate a translationally regulated non-autonomous mitochondrial stress response mechanism in the modulation of lifespan by insulin-like signaling and S6K.

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Anticorpo monoclonale ANTI-FLAG® M2, 1 mg/mL, clone M2, affinity isolated antibody, buffered aqueous solution (50% glycerol, 10 mM sodium phosphate, and 150 mM NaCl, pH 7.4)
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5-Fluorouracil, ≥99% (HPLC), powder
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Anti-α-tubulina monoclonale, clone B-5-1-2, purified from hybridoma cell culture