Researchers have identified a key molecular mechanism behind the health benefits of calorie restriction or reduced food intake without malnutrition.
Dietary restriction is best known for its ability to slow ageing in laboratory animals, researchers said.
The study led by Harvard School of Public Health (HSPH) shows that restricting two amino acids, methionine and cysteine, results in increased hydrogen sulfide (H2S) production and protection against ischemia reperfusion injury, damage to tissue that occurs following the interruption of blood flow as during organ transplantation and stroke.
Increased H2S production upon dietary restriction was also associated with lifespan extension in worms, flies, and yeast.
Although H2S gas is extremely toxic in high amounts, low levels present in naturally occurring sulphur springs have long been associated with health benefits.
“This finding suggests that H2S is one of the key molecules responsible for the benefits of dietary restriction in mammals and lower organisms as well,” said senior author James Mitchell.
“While more experiments are required to understand how H2S exerts its beneficial effects, it does give us a new perspective on which molecular players to target therapeutically in our efforts to combat human disease and ageing,” said Mitchell.
Dietary restriction is known to have beneficial health effects, including protection from tissue injury and improved metabolism. It has also been shown to extend the lifespan of multiple model organisms, ranging from yeast to primates.
Researchers demonstrated that one week of dietary restriction increased antioxidant responses and protected mice from liver ischemia reperfusion injury, but surprisingly, this protective effect was intact even in animals that could not mount such an antioxidant response.
Instead, the researchers found that the protection required increased production of H2S, which occurred upon reduction of dietary intake of the two sulphur-containing amino acids, methionine and cysteine.
When the diet was supplemented with these two amino acids, increased H2S production and dietary restriction benefits were both lost.
“These findings give us a better understanding of how dietary interventions extend lifespan and protect against injury. More immediately, they could have important implications for what to eat and not to eat before a planned acute stress like surgery, when the risk of ischemic injury can be relatively high,” said Hine.
The study appears in the journal Cell.