Could hydrogen sulfide hold the key to a long life?

December 03, 2007

SEATTLE - 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 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 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.
-end-
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 fhcrc.org.

Fred Hutchinson Cancer Research Center

Related Nematodes Articles from Brightsurf:

Oil-eating worms provide valuable assistance in soil remediation
Bionanotechnology Lab of Kazan Federal University works on adapting nematodes to consuming oil waste.

Fungal species naturally suppresses cyst nematodes responsible for major sugar beet losses
In the current study, the authors showed that similar fungi inhabited sugar beet fields in California, suggesting that a group of naturally occurring fungi, given the right conditions, might be able to dramatically reduce nematode populations in one season.

The balancing act between plant growth and defense
Kumamoto University researchers have pinpointed the mechanism that regulates the balance between plant growth and defense.

Fungus application thwarts major soybean pest, study finds
The soybean cyst nematode sucks the nutrients out of soybean roots, causing more than $1 billion in soybean yield losses in the U.S. each year.

WSU genetic discovery holds implications for better immunity, longer life
Wrinkles on the skin of a microscopic worm might provide the key to a longer, healthier life for humans.

How nematodes outsmart the defenses of pests
The western corn rootworm, one of the world's most damaging maize pests, can use plant defense compounds to defend itself against its own natural enemies, so-called entomopathogenic nematodes.

Research suggests fumigants have very low long-term impact on soil health
It started with curiosity. How does a fumigant, commonly used for nematode management in potato cropping systems, influence soil microbial communities?

New survey confirms muscadine grapes are affected by parasitic nematodes
Muscadines are also known for being hearty grapes, with a tough skin that protects them from many fungal diseases.

Otherworldly worms with three sexes discovered in Mono Lake
The extreme environment of Mono Lake was thought to only house two species of animals -- until now.

New information on regulation of sense of smell with the help of nematodes
PIM kinases are enzymes that are evolutionarily well conserved in both humans and nematodes.

Read More: Nematodes News and Nematodes Current Events
Brightsurf.com is a participant in the Amazon Services LLC Associates Program, an affiliate advertising program designed to provide a means for sites to earn advertising fees by advertising and linking to Amazon.com.