Functional loss of two ceramide synthases elicits autophagy-dependent lifespan extension in C. elegans.
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 la...
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2013
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oai:doaj.org-article:123aa8c456f54949a4d4d820ae3406a62021-11-18T09:03:44ZFunctional loss of two ceramide synthases elicits autophagy-dependent lifespan extension in C. elegans.1932-620310.1371/journal.pone.0070087https://doaj.org/article/123aa8c456f54949a4d4d820ae3406a62013-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/23894595/?tool=EBIhttps://doaj.org/toc/1932-6203Ceramide 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.Mai-Britt MosbechRikke KruseEva Bang HarvaldAnne Sofie Braun OlsenSandra Fernandez GallegoHans Kristian Hannibal-BachChrister S EjsingNils J FærgemanPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 8, Iss 7, p e70087 (2013) |
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Medicine R Science Q Mai-Britt Mosbech Rikke Kruse Eva Bang Harvald Anne Sofie Braun Olsen Sandra Fernandez Gallego Hans Kristian Hannibal-Bach Christer S Ejsing Nils J Færgeman Functional loss of two ceramide synthases elicits autophagy-dependent lifespan extension in C. elegans. |
| description |
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. |
| format |
article |
| author |
Mai-Britt Mosbech Rikke Kruse Eva Bang Harvald Anne Sofie Braun Olsen Sandra Fernandez Gallego Hans Kristian Hannibal-Bach Christer S Ejsing Nils J Færgeman |
| author_facet |
Mai-Britt Mosbech Rikke Kruse Eva Bang Harvald Anne Sofie Braun Olsen Sandra Fernandez Gallego Hans Kristian Hannibal-Bach Christer S Ejsing Nils J Færgeman |
| author_sort |
Mai-Britt Mosbech |
| title |
Functional loss of two ceramide synthases elicits autophagy-dependent lifespan extension in C. elegans. |
| title_short |
Functional loss of two ceramide synthases elicits autophagy-dependent lifespan extension in C. elegans. |
| title_full |
Functional loss of two ceramide synthases elicits autophagy-dependent lifespan extension in C. elegans. |
| title_fullStr |
Functional loss of two ceramide synthases elicits autophagy-dependent lifespan extension in C. elegans. |
| title_full_unstemmed |
Functional loss of two ceramide synthases elicits autophagy-dependent lifespan extension in C. elegans. |
| title_sort |
functional loss of two ceramide synthases elicits autophagy-dependent lifespan extension in c. elegans. |
| publisher |
Public Library of Science (PLoS) |
| publishDate |
2013 |
| url |
https://doaj.org/article/123aa8c456f54949a4d4d820ae3406a6 |
| work_keys_str_mv |
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