Pathways Underlying the Benefits of Calorie Restriction

NIH | JANUARY 27, 2015

Calorie restriction is the process of reducing food intake—typically by at least 30% from a normal diet—without malnutrition. This regimen, also referred to as dietary restriction, has numerous health benefits. It can extend the lifespan, can also improve tolerance to certain metabolic stresses to the body.

A team at the Harvard School of Public Health set out to determine the molecular mechanisms by which calorie restriction can bring health benefits.

The researchers induced surgical stress in mice by temporarily halting blood flow to the liver. When blood flow is restored to the tissue, it shows damage and inflammation. This injury model, known as ischemia reperfusion, is similar to what occurs during organ transplantation, stroke, or heart attack in humans.

The team found that mice that had their diet restricted by 50% for a week before the surgery showed less liver damage than mice provided with unlimited food. The beneficial effects of the calorie restriction could be blocked, however, by providing the mice with extra methionine and cysteine. These 2 amino acids are notable because they both contain sulfur.

The scientists determined that restricting these 2 sulfur-containing amino acids activated a metabolic pathway called the transsulfuration pathway, which resulted in increased production of the gas hydrogen sulfide (H2S). When they deleted a gene for an H2S-producing enzyme in mice, the protective effects of dietary restriction were lost.

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