Pathways Underlying the Benefits of Calorie Restriction

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. Conversely, mice genetically manipulated to make more of the gas had less surgical damage, even without dietary intervention. Thus, production of the gas was important for the benefits of calorie restriction against surgical stress.


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