3-Ketoacyl thiolase delays aging of Caenorhabditis elegans and is required for lifespan extension mediated by sir-2.1
| Autor: | Konstantinos Boulias, Leonard Guarente, Simona Nedelcu, Alina Berdichevsky, Nicholas A. Bishop, H. Robert Horvitz |
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| Rok vydání: | 2010 |
| Předmět: |
Premature aging
Aging Mutant medicine.disease_cause Lipofuscin Progeria medicine Animals Sirtuins Caenorhabditis elegans Caenorhabditis elegans Proteins Gene Genetics Mutation Multidisciplinary biology Thiolase Fatty Acids Aging Premature Biological Sciences Acetyl-CoA C-Acyltransferase biology.organism_classification medicine.disease Oxidation-Reduction Genetic screen |
| Zdroj: | Proceedings of the National Academy of Sciences. 107:18927-18932 |
| ISSN: | 1091-6490 0027-8424 |
| DOI: | 10.1073/pnas.1013854107 |
| Popis: | Studies of long-lived Caenorhabditis elegans mutants have identified several genes that function to limit lifespan, i.e., loss-of-function mutations in these genes promote longevity. By contrast, little is known about genes that normally act to delay aging and that when mutated cause premature aging (progeria). To seek such genes, we performed a genetic screen for C. elegans mutants that age prematurely. We found that loss-of-function mutations of the ketoacyl thiolase gene kat-1 result in an increased accumulation of the lipofuscin-like fluorescent aging pigment, shortened lifespan, early behavioral decline, and other abnormalities characteristic of premature aging. These findings suggest that kat-1 acts to delay C. elegans aging. kat-1 encodes a conserved metabolic enzyme that catalyzes the last step of fatty acid oxidation and was previously shown to regulate fat accumulation in worms. We observed that kat-1 is required for the extension of lifespan and enhanced thermotolerance mediated by extra copies of the deacetylase gene sir-2.1 . kat-1 acts independently of other known pathways that affect longevity. Our findings suggest that defects in fatty acid oxidation can limit lifespan and accelerate aging in C. elegans and that kat-1 -mediated fatty acid oxidation is crucial for overexpressed sir-2.1 to delay aging. |
| Databáze: | OpenAIRE |
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