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...
| Main Authors: | , , , , , |
|---|---|
| Other Authors: | |
| Format: | Article |
| Language: | en_US |
| Published: |
National Academy of Sciences
2011
|
| 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 |
| Summary: | 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. |
|---|