論文 - 詳細
| RRC ID | 55871 |
|---|---|
| 著者 | Dalton HM, Curran SP. |
| タイトル | Hypodermal responses to protein synthesis inhibition induce systemic developmental arrest and AMPK-dependent survival in Caenorhabditis elegans. |
| ジャーナル | PLoS Genet |
| 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 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. |
| 巻・号 | 14(7) |
| ページ | e1007520 |
| 公開日 | 2018-7-1 |
| DOI | 10.1371/journal.pgen.1007520 |
| PII | PGENETICS-D-18-00419 |
| PMID | 30020921 |
| PMC | PMC6066256 |
| MeSH | AMP-Activated Protein Kinases / genetics AMP-Activated Protein Kinases / metabolism* Aging / drug effects Aging / physiology Animals Biological Evolution Caenorhabditis elegans / physiology* Caenorhabditis elegans Proteins / genetics Caenorhabditis elegans Proteins / metabolism* Feeding Behavior / physiology Gene Expression Regulation, Developmental / physiology* Larva / physiology Longevity / drug effects Longevity / genetics Pharynx / physiology Protein Biosynthesis / drug effects Protein Biosynthesis / genetics Protein Biosynthesis / physiology* Protein Synthesis Inhibitors / pharmacology RNA Interference Ribosomes / drug effects Ribosomes / genetics Ribosomes / metabolism Signal Transduction / genetics Subcutaneous Tissue / metabolism |
| IF | 5.224 |
| 引用数 | 6 |
| オルトメトリクス指標 |
オルトメトリクス指標項目
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| 最多言及媒体 | X(Twitter) |
| 各媒体での言及数の合計 | 6 |
| 過去6か月間でのオルトメトリクス指標の変動値 | 0.0 |
| リソース情報 | |
| 線虫 | tm1770 |