Researchers at Fred Hutchinson Cancer Research Center have found that hydrogen sulfide, or H2S, the chemical that gives rotten eggs their sulfurous stench, significantly increased life span and heat tolerance in the nematode worm, or C. elegans, whose biology is similar in many respects to that of humans.
The study was conducted 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.
AdvertisementPreviously, researchers successfully used the same compound to put mice into a state of reversible metabolic hibernation.
In order to understand the mechanisms by which hydrogen sulfide induces hibernation in mice, the research team used the tiny nematode, as 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 research team found 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.
"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.
The findings have appeared in the PNAS Online Early Edition, a publication of the Proceedings of the National Academy of Sciences of the United States of America.
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