Study finds 'rotten egg' chemical increases life span and heat tolerance in
worms
SEATTLE, Dec. 3 /PRNewswire/ -- Hydrogen sulfide, or H2S, the chemical
that gives rotten eggs their sulfurous stench -- and the same compound that
researchers at Fred Hutchinson Cancer Research Center successfully have
used to put mice into a state of reversible metabolic hibernation -- has
now been shown to significantly increase life span and heat tolerance in
the nematode worm, or C. elegans.
These findings by Mark Roth, Ph.D., a member of the Center's Basic
Sciences Division, and Dana Miller, Ph.D., a postdoctoral research fellow
in Roth's lab, appear in the PNAS Online Early Edition, a publication of
the Proceedings of the National Academy of Sciences of the United States of
America.
In an effort to understand the mechanisms by which hydrogen sulfide
induces hibernation in mice, the researchers turned to the tiny nematode, a
workhorse of laboratory science because its biology is similar in many
respects to that of humans. For example, like humans, nematodes have a
central nervous system and the ability to reproduce. The worms also are
ideally suited for studying life span, because they normally live for only
two to three weeks.
The researchers found, to their surprise, that nematodes that were
raised in a carefully controlled atmosphere with low concentrations of H2S
(50 parts per million in room air) did not hibernate. Instead, their
metabolism and reproductive activity remained normal, their life span
increased and they became more tolerant to heat than untreated worms.
The H2S-exposed worms lived eight times longer than untreated worms
when moved from normal room air (22 C or 70 F) to a high-temperature
environment (35 C or 95 F). Roth and colleagues replicated these results in
15 independent experiments.
"Although the maximum extension of survival time varied between
experiments, the effect was quite robust. On average, 77 percent of the
worms exposed to H2S outlived the untreated worms," Roth said. The mean
life span of worms grown in an atmosphere laced with hydrogen sulfide was
9.6 days greater than that of the untreated population, a longevity
increase of 70 percent.
Most genes that influence life span in C. elegans act on one of three
genetic pathways: those that control insulin/IGF (insulin growth factor)
signaling, those that control mitochondrial function and those that
modulate the effects of dietary restriction.
Roth and colleagues ruled out hydrogen sulfide's influence on each of
these pathways. Instead, they suspect it acts through a different
mechanism. One theory is that exposure to H2S naturally regulates the
activity of a gene called SIR-2.1, which has been shown to influence life
span in many organisms, including the nematode. Previous studies have found
that over-expression of this gene increases the longevity of C. elegans by
18 percent to 20 percent.
"Further research into the genetic mechanisms that influence
H2S-induced changes in nematodes may reveal similar mechanisms in higher
organisms, including humans, with potentially wide-ranging implications in
both basic research and clinical practice," Roth said. For example,
understanding how H2S affects physiology in animals may lead to the
development of drugs that could delay the onset of age-related diseases in
humans such as cancer, Alzheimer's and heart disease.
Roth's hibernation research made headlines worldwide in April 2005 when
he was the first to show that exposing mice to minute amounts of hydrogen
sulfide could induce a state of reversible "hibernation on demand,"
dramatically reducing their core body temperature, respiration and need for
oxygen. Roth envisions a future in which similar techniques could be used
to "buy time" for critically ill patients who otherwise would face injury
and death from insufficient blood and oxygen supply to organs and tissues.
Roth hypothesizes that H2S, a chemical normally produced in humans and
animals, may help regulate body temperature and metabolic activity.
Hydrogen sulfide is similar to oxygen at the molecular level because it
binds at many of the same proteins. As a result, H2S competes for and
interferes with the body's ability to use oxygen for energy production -- a
process within the cell's power-generating machinery called oxidative
phosphorylation.
The inhibition of this function, in turn, is what Roth and colleagues
believe causes organisms such as mice to shut down metabolically and enter
a hibernation-like state pending re-exposure to normal room air, after
which they quickly regain normal function and metabolic activity with no
long-term negative effects.
The National Institutes of Health, the NIH Center for Research
Resources, the Caenorhabditis Genetics Center and a National Research
Service Award Fellowship supported this work.
At Fred Hutchinson Cancer Research Center, our interdisciplinary teams
of world-renowned scientists and humanitarians work together to prevent,
diagnose and treat cancer, HIV/AIDS and other diseases. Our researchers,
including three Nobel laureates, bring a relentless pursuit and passion for
health, knowledge and hope to their work and to the world. For more
information, please visit http://www.fhcrc.org.
CONTACT
Kristen Woodward
(206) 667-5095
kwoodwar@fhcrc.org
SOURCE Fred Hutchinson Cancer Research Center
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Related links:
http://www.fhcrc.org
CONTACT:
Kristen Woodward of Fred Hutchinson Cancer
Research Center, +1-206-667-5095, kwoodwar@fhcrc.org
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