Hydrogen sulfide -- maligned for its toxic and explosive properties -- may slow aging and block damaging chemical reactions inside cells, according to scientists in China, who reviewed studies on the malodorous gas and its effects on the cardiovascular and nervous systems.
Hydrogen sulfide activates a gene implicated in longevity in a similar way to resveratrol, an antioxidant in red wine that GlaxoSmithKline tried unsuccessfully to turn into a drug, scientists found. Unlike resveratrol, hydrogen sulfide is made by the body. Pills that boost levels of the compound may one day prolong life while tapping into a dietary supplement market that's worth $28 billion a year in the United States alone.
"Everyone always thought of hydrogen sulfide as the bad guy -- an environmental pollutant, a toxin," said Matt Whiteman, associate professor of experimental therapeutics at England's University of Exeter. Since the discovery that the gas is made in mammalian cells, "this research area has exploded," he said.
Increasing longevity is one of humanity's greatest achievements, Babatunde Osotimehin, executive director of the United Nations Population Fund, said in a report on aging last year. There were almost 810 million people older than 60 years on the planet in 2012, up from 205 million in 1950.
"There is a lot of interest in understanding how we age and, as human beings, it's natural for us to question if we could prolong life potentially by delaying aging," said John Rouse, professor of chromosome biology at Scotland's University of Dundee. Hydrogen sulfide is a worthy target, said Rouse, who studies DNA repair and aging.
Colorless and flammable, hydrogen sulfide was used briefly in warfare during the First World War as a chemical weapon. Over a certain threshold, it's toxic, Rouse said, "but below that, there are certain health benefits."
Hydrogen sulfide appears to slow aging and aging-related diseases in at least three main ways, said Jiang Zhisheng and colleagues at the University of South China in Hengyang City, Hunan, in a report slated for publication next month in the journal Molecular and Cellular Biology. The gas helps counter cell-damaging free-radicals; encourages production of an enzyme thought to be a regulator of lifespan; and interacts with a gene that appears to have its own market basket of anti-aging activity.
"Data available so far strongly suggest that hydrogen sulfide may become the next potent agent for preventing and ameliorating the symptoms of aging and age-associated diseases," Jiang said, adding that people may one day take hydrogen sulfide-rich food or supplements to slow aging.
The gas has a role for regulating blood pressure, improving the flexibility of veins and arteries and producing a smoother flow of blood, researchers from the University of Exeter's Peninsula Medical School and King's College London said in study in the journal Circulation published in 2008. Whiteman and fellow University of Exeter researchers showed the following year that decreases in hydrogen sulfide may contribute to vascular complications in diabetics.
"Precisely how hydrogen sulfide does its business is not clear, and that's also exciting," Whiteman said, adding that early research on hydrogen sulfide focused on its toxic effects.
"It was assumed that any hydrogen sulfide in the body would be bad," he said. "However, it's now emerging that the body actually produces hydrogen sulfide by specific enzymes and, as more researchers become interested in this gas, we are finding changes in hydrogen sulfide synthesis or changes in how hydrogen sulfide is used by the body."
The gas appears to switch on klotho, a gene named after one of the mythical Greek fates who controlled the length of human life. Klotho is thought to extend lifespan via a number of different pathways, some of which promote production of the body's own antioxidants, Jiang and colleagues said in their report. On the other hand, low levels of hydrogen sulfide are associated with high blood pressure, Parkinson's disease and Alzheimer's disease, it said.
One of the main advantages of hydrogen sulfide may be its ability to activate the SIRT1 enzyme, a so-called skinny gene that mimics the effect of caloric restriction, the University of Dundee's Rouse said. There is good evidence that limiting food delays aging as the body generates fewer free radicals that cause wear and tear on the body, he said.
"There's mounting evidence that hydrogen sulfide can counteract free radicals," Rouse said, adding that people who suffer from inflammatory or autoimmune disease have long lauded the benefits of bathing in volcanic springs, a rich source of the sulfurous gas.
Glaxo was working on a similar SIRT1 approach with resveratrol until 2010, when its experimental drug was shown not to provide sufficient benefit to cancer patients and that it may have damaged kidneys. The London-based drugmaker began the research following its $720 million purchase of Sirtris Pharmaceuticals Inc. in 2008.
Sirtris co-founder David Sinclair and colleagues tested about 500,000 molecules more than five years ago for their ability to activate SIRT1, the enzyme credited with resveratrol's ability to extend lifespan by 30 to 70 percent in organisms from yeast and worms to flies and mice.
Hydrogen sulfide may prove challenging as an anti-aging therapy as well. Progress is limited by the availability of tools and compounds that can generate the gas in an appropriate manner, the University of Exeter's Whiteman said.
"Enzymes make hydrogen sulfide slowly, so we should really be using tools that make it slowly," he said.
Diets rich in onions, garlic and other Allium plants are loaded with potential compounds that can release or generate hydrogen sulfide, Whiteman said. Still, there's no evidence yet that garlic's health benefits are derived from hydrogen sulfide.
"It could possibly, but there are a lot of other things in garlic as well," he said, adding that what's already known about the gas is spurring on research.
"In the space of about 10 years, it's gone from there being sessions at conferences on hydrogen sulfide to full-grown conferences where only hydrogen sulfide is talked about," Whiteman said. "It's made a massive leap."
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