A great deal of effort over the past fifteen years has gone into efforts to fully understand how calorie restriction works to improve health and extend life. The research community would like to have sufficient knowledge to produce drugs that mimic this effect. At this point what researchers have is still a sketch, however: near everything in the operation of metabolism changes in response to reduced calorie intake, which has made it very challenging to figure out cause and effect. Meanwhile, new aspects of calorie restriction biochemistry are discovered on a regular basis these days, with no signs of an end in sight. Researchers here find that one of the benefits provided by calorie restriction is not, as thought, due to increased cellular antioxidant responses, but instead involves hydrogen sulfide (H2S) in some yet to be identified way:
Dietary restriction is a type of intervention that can include reduced overall food intake, decreased consumption of particular macronutrients such as protein, or intermittent bouts of fasting. It 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. The molecular explanations for these effects are not completely understood, but were thought to require protective antioxidant responses activated by the mild oxidative stress caused by dietary restriction itself.
[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 sulfur-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. The investigators also found that genes involved in H2S production were also required for longevity benefits of dietary restriction in other organisms, including yeast, worms, and flies.
Mammalian cells [produce] low levels of H2S, but this is the first time that this molecule has been linked directly to the health benefits of dietary restriction. "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. 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 aging."