論文 - 詳細
| RRC ID | 46091 |
|---|---|
| 著者 | Mosbech MB, Kruse R, Harvald EB, Olsen AS, Gallego SF, Hannibal-Bach HK, Ejsing CS, Færgeman NJ. |
| タイトル | Functional loss of two ceramide synthases elicits autophagy-dependent lifespan extension in C. elegans. |
| ジャーナル | PLoS One |
| Abstract |
Ceramide and its metabolites constitute a diverse group of lipids, which play important roles as structural entities of biological membranes as well as regulators of cellular growth, differentiation, and development. The C. elegans genome comprises three ceramide synthase genes; hyl-1, hyl-2, and lagr-1. HYL-1 function is required for synthesis of ceramides and sphingolipids containing very long acyl-chains (≥C24), while HYL-2 is required for synthesis of ceramides and sphingolipids containing shorter acyl-chains (≤C22). Here we show that functional loss of HYL-2 decreases lifespan, while loss of HYL-1 or LAGR-1 does not affect lifespan. We show that loss of HYL-1 and LAGR-1 functions extend lifespan in an autophagy-dependent manner, as knock down of the autophagy-associated gene ATG-12 abolishes hyl-1;lagr-1 longevity. The transcription factors PHA-4/FOXA, DAF-16/FOXO, and SKN-1 are also required for the observed lifespan extension, as well as the increased number of autophagosomes in hyl-1;lagr-1 animals. Both autophagic events and the transcription factors PHA-4/FOXA, DAF-16, and SKN-1 have previously been associated with dietary restriction-induced longevity. Accordingly, we find that hyl-1;lagr-1 animals display reduced feeding, increased resistance to heat, and reduced reproduction. Collectively, our data suggest that specific sphingolipids produced by different ceramide synthases have opposing roles in determination of C. elegans lifespan. We propose that loss of HYL-1 and LAGR-1 result in dietary restriction-induced autophagy and consequently prolonged longevity. |
| 巻・号 | 8(7) |
| ページ | e70087 |
| 公開日 | 2013-1-1 |
| DOI | 10.1371/journal.pone.0070087 |
| PII | PONE-D-13-05905 |
| PMID | 23894595 |
| PMC | PMC3716707 |
| MeSH | Animals Autophagy* / genetics Caenorhabditis elegans / enzymology* Caenorhabditis elegans / genetics Caenorhabditis elegans / growth & development* Caenorhabditis elegans Proteins* / genetics Caenorhabditis elegans Proteins* / metabolism DNA-Binding Proteins / genetics DNA-Binding Proteins / metabolism Forkhead Transcription Factors Gene Knockdown Techniques Lipid Metabolism Longevity* / genetics Oxidoreductases / deficiency* Oxidoreductases / genetics Oxidoreductases / metabolism Phenotype Small Ubiquitin-Related Modifier Proteins / genetics Small Ubiquitin-Related Modifier Proteins / metabolism Trans-Activators / genetics Trans-Activators / metabolism Transcription Factors / genetics Transcription Factors / metabolism |
| IF | 2.74 |
| 引用数 | 26 |
| WOS 分野 | BIOCHEMISTRY & MOLECULAR BIOLOGY |
| 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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| 各媒体での言及数の合計 | 0 |
| 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 | tm2031 |