Hypodermal responses to protein synthesis inhibition induce systemic developmental arrest and AMPK-dependent survival in Caenorhabditis elegans.

PLoS Genetics
Hans M Dalton, Sean P Curran

Abstract

Across organisms, manipulation of biosynthetic capacity arrests development early in life, but can increase health- and lifespan post-developmentally. Here we demonstrate that this developmental arrest is not sickness but rather a regulated survival program responding to reduced cellular performance. We inhibited protein synthesis by reducing ribosome biogenesis (rps-11/RPS11 RNAi), translation initiation (ifg-1/EIF3G mutation and egl-45/EIF3A RNAi), or ribosome progression (cycloheximide treatment), all of which result in a specific arrest at larval stage 2 of C. elegans development. This quiescent state can last for weeks-beyond the normal C. elegans adult lifespan-and is reversible, as animals can resume reproduction and live a normal lifespan once released from the source of protein synthesis inhibition. The arrest state affords resistance to thermal, oxidative, and heavy metal stress exposure. In addition to cell-autonomous responses, reducing biosynthetic capacity only in the hypodermis was sufficient to drive organism-level developmental arrest and stress resistance phenotypes. Among the cell non-autonomous responses to protein synthesis inhibition is reduced pharyngeal pumping that is dependent upon AMPK-mediated signal...Continue Reading

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Citations

Oct 16, 2019·Proceedings of the National Academy of Sciences of the United States of America·James D NhanSean P Curran
Nov 8, 2020·Communications Biology·Nicole L Stuhr, Sean P Curran

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Methods Mentioned

BETA
environmental stress
reverse transcription PCR
fluorescence microscopy
Assay

Software Mentioned

ZEN
Fiji
ImageJ
JMP Pro
R
Excel

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