New link between diet and lifespan
25 May 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 journal
Nature , 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
“It is well known that if you put C. elegans on a
restricted diet, you can extend its lifespan by 40 to 50%,” 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,”
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 of
C. 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.
1. Lucanic, Jason M Held, Maithili C Vantipalli, Ida
M Klang, Jill B Graham, Bradford W Gibson, Gordon J Lithgow, Matthew
S Gill. N-Acylethanolamine Signaling Mediates the Effect of Diet on
Lifespan in C. elegans. Nature, 12 May 2011.