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Scripps Research scientist identifies new
pathway affecting lifespan...New discovery
advances study of diet and longevity
May 12, 2011 – A team led by a scientist
from the Florida campus of The Scripps
Research Institute has identified a new role
for a biological pathway that not only
signals the body's metabolic response to
nutritional changes, but also affects
lifespan.
The study, published in the May 12, 2011
issue of the journalNature, was conducted on Caenorhabditis
elegans (nematodes
or roundworms), which are a widely accepted
model for human aging research.
"Not only have we been able to identify some
of these molecules for the first time in the
worm, but we have also been able to show
they act as a signal of nutrient
availability and ultimately influence the
worm's lifespan," said Matthew Gill, PhD.
Gill, an assistant professor in the Scripps
Research Department of Metabolism and Aging,
conducted the research while at The Buck
Institute for Research on Aging in Novato,
California.
"What makes this important is that the same
molecules are present in both humans and C.
elegans, so these molecules may play similar
roles in both organisms."
Dietary restriction is a well-known means of
extending lifespan and postponing
age-related disease in many species,
including yeast, worms, flies, and rodents.
However, until this study, little was known
about the molecular signals involved.
The molecules identified in the new study
are N-acylethanolamines (NAEs), a group of
signaling molecules derived from lipids that
help indicate nutrient availability in the
environment and maintain an animal's
internal energy balance. In the study, Gill
and his colleagues showed that NAE abundance
in the worm is reduced during periods of
dietary restriction, and that NAE deficiency
in the presence of abundant food is
sufficient to extend the animal's lifespan.
"It is well known that if you put C.
elegans on
a restricted diet, you can extend its
lifespan by 40 to 50 percent," Gill said.
"However, we were amazed to see that if you
add back just one of these NAE molecules,
eicosapentaenoyl ethanolamide, it completely
abrogates the lifespan extension."
Importantly, this particular NAE is similar
to endocannabinoids in mammals, which
regulate many different physiological
processes including nutrient intake and
energy balance, as well as inflammation and
neuronal function. "The identification of
other components of a novel endocannabinoid
system in the worm now brings a new model
system to the many researchers studying NAE
and endocannabinoid physiology," said Gill.
Intriguingly, the study also established a
link among fat, NAE levels, and longevity.
Other studies in rodents have shown that the
availability of fatty acids can influence
NAE levels. However, Gill and his colleagues
found that in a genetically altered strain
ofC. elegans the
inability to produce certain polyunsaturated
fatty acids was not only associated with a
reduction in levels of specific NAEs but
also with lifespan extension. He added that
the study's findings could shape future drug
development efforts to influence aging and
age-related disease.
###
The first author of the study, "N-Acylethanolamine
Signaling Mediates the Effect of Diet on
Lifespan in C.
elegans," is Mark Lucanic, a postdoctoral
fellow at the Buck Institute for Research on
Aging. Other authors include Jason M. Held,
Maithili C Vantipalli, Jill B. Graham,
Bradford W. Gibson, and Gordon J. Lithgow of
the Buck Institute for Research on Aging;
and Ida M. Klang of the Buck Institute for
Research on Aging and the Karolinska
Institute.
The study was supported by the Larry L.
Hillblom Foundation and the National
Institutes of Health.
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