%0 Journal Article
%T Hypodermal responses to protein synthesis inhibition induce systemic developmental arrest and AMPK-dependent survival in Caenorhabditis elegans
%A Hans M. Dalton
%A Sean P. Curran
%J -
%D 2018
%R 10.1371/journal.pgen.1007520
%X 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¡ªbeyond the normal C. elegans adult lifespan¡ªand 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 signaling. The reduced pharyngeal pumping in response to protein synthesis inhibition is recapitulated by exposure to microbes that generate protein synthesis-inhibiting xenobiotics, which may mechanistically reduce ingestion of pathogen and toxin. These data define the existence of a transient arrest-survival state in response to protein synthesis inhibition and provide an evolutionary foundation for the conserved enhancement of healthy aging observed in post-developmental animals with reduced biosynthetic capacity
%K Protein synthesis
%K RNA interference
%K Caenorhabditis elegans
%K Thermal stresses
%K Hypodermis
%K Phenotypes
%K Streptomyces
%K Heavy metals
%U https://journals.plos.org/plosgenetics/article?id=10.1371/journal.pgen.1007520