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 degrees Celsius, 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.
|