3-Ketoacyl thiolase delays aging of Caenorhabditis elegans and is required for lifespan extension mediated by sir-2.1
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 a...
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| Format: | Article |
| Language: | en_US |
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National Academy of Sciences
2011
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| Online Access: | http://hdl.handle.net/1721.1/64811 https://orcid.org/0000-0002-9964-9613 https://orcid.org/0000-0003-4064-2510 https://orcid.org/0000-0002-5117-3994 |
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| author | Berdichevsky, Alina Nedelcu, Simona Boulias, Konstantinos Bishop, Nicholas A. Guarente, Leonard Pershing Horvitz, Howard Robert |
| author2 | Massachusetts Institute of Technology. Department of Biology |
| author_facet | Massachusetts Institute of Technology. Department of Biology Berdichevsky, Alina Nedelcu, Simona Boulias, Konstantinos Bishop, Nicholas A. Guarente, Leonard Pershing Horvitz, Howard Robert |
| author_sort | Berdichevsky, Alina |
| collection | MIT |
| description | 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. |
| first_indexed | 2024-09-23T15:18:18Z |
| format | Article |
| id | mit-1721.1/64811 |
| institution | Massachusetts Institute of Technology |
| language | en_US |
| last_indexed | 2024-09-23T15:18:18Z |
| publishDate | 2011 |
| publisher | National Academy of Sciences |
| record_format | dspace |
| spelling | mit-1721.1/648112022-10-02T02:02:14Z 3-Ketoacyl thiolase delays aging of Caenorhabditis elegans and is required for lifespan extension mediated by sir-2.1 Berdichevsky, Alina Nedelcu, Simona Boulias, Konstantinos Bishop, Nicholas A. Guarente, Leonard Pershing Horvitz, Howard Robert Massachusetts Institute of Technology. Department of Biology Paul F. Glenn Center for Biology of Aging Research (Massachusetts Institute of Technology) Horvitz, H. Robert Berdichevsky, Alina Nedelcu, Simona Boulias, Konstantinos Bishop, Nicholas A. Guarente, Leonard Pershing Horvitz, H. Robert 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. Ellison Medical Foundation National Institutes of Health (U.S.) Paul F. Glenn Foundation 2011-07-14T17:39:30Z 2011-07-14T17:39:30Z 2010-11 2010-09 Article http://purl.org/eprint/type/JournalArticle 0027-8424 1091-6490 http://hdl.handle.net/1721.1/64811 Berdichevsky, A. et al. “3-Ketoacyl Thiolase Delays Aging of Caenorhabditis Elegans and Is Required for Lifespan Extension Mediated by Sir-2.1.” Proceedings of the National Academy of Sciences 107.44 (2010) : 18927-18932. Web. 14 July 2011. https://orcid.org/0000-0002-9964-9613 https://orcid.org/0000-0003-4064-2510 https://orcid.org/0000-0002-5117-3994 en_US http://dx.doi.org/10.1073/pnas.1013854107 Proceedings of the National Academy of Sciences of the United States of America Article is made available in accordance with the publisher's policy and may be subject to US copyright law. Please refer to the publisher's site for terms of use. application/pdf National Academy of Sciences PNAS |
| spellingShingle | Berdichevsky, Alina Nedelcu, Simona Boulias, Konstantinos Bishop, Nicholas A. Guarente, Leonard Pershing Horvitz, Howard Robert 3-Ketoacyl thiolase delays aging of Caenorhabditis elegans and is required for lifespan extension mediated by sir-2.1 |
| title | 3-Ketoacyl thiolase delays aging of Caenorhabditis elegans and is required for lifespan extension mediated by sir-2.1 |
| title_full | 3-Ketoacyl thiolase delays aging of Caenorhabditis elegans and is required for lifespan extension mediated by sir-2.1 |
| title_fullStr | 3-Ketoacyl thiolase delays aging of Caenorhabditis elegans and is required for lifespan extension mediated by sir-2.1 |
| title_full_unstemmed | 3-Ketoacyl thiolase delays aging of Caenorhabditis elegans and is required for lifespan extension mediated by sir-2.1 |
| title_short | 3-Ketoacyl thiolase delays aging of Caenorhabditis elegans and is required for lifespan extension mediated by sir-2.1 |
| title_sort | 3 ketoacyl thiolase delays aging of caenorhabditis elegans and is required for lifespan extension mediated by sir 2 1 |
| url | http://hdl.handle.net/1721.1/64811 https://orcid.org/0000-0002-9964-9613 https://orcid.org/0000-0003-4064-2510 https://orcid.org/0000-0002-5117-3994 |
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