Experiments with mice have shown that a 25% reduction in calories activated a single enzyme, Sirt3, which helped preserve hearing. The experiments are described by researches in the journal Cell.
"If we can find compounds that activate Sirt3 we may be able to obtain some of the benefits of caloric restriction without having to restrict our calories," said Tomas A. Prolla, a professor of genetics at University of Wisconsin-Madison in the US and senior author of the new paper.
Prolla and his colleagues carried out experiments with normal mice and mice deprived of the Sirt3 enzyme. In one experiment both groups were fed the 25%-reduced calorie diet for 10 months. The diet had the same weight loss effect on both groups.
Although the diet delayed hearing loss at various frequencies in the normal mice, it did not work at all in the mice lacking Sirt3.
Energy factories and free radicals
The experiments also suggested how the benefits of caloric restriction play out at the molecular level.
"What seems to happen that drives caloric restriction is that the organism senses it is under stress," Prolla explained. "There are then metabolic changes that favour self-preservation."
Under normal conditions, he said, levels of Sirt3 are low. Caloric restriction appears to boost levels of Sirt3 and the boost helps the cells' energy factories, called mitochondria.
The mitochondria produce not only the energy, but also atoms called free radicals, which damage cells and advance the effects of aging. When Sirt3 levels rise, however, they reduce production of the harmful free radicals. One result is less damage to cells, including the cells of the inner ear.
"We need to find out which are the main mediators of caloric restriction," Prolla said, explaining that the current study indicates Sirt3 is one of them. "Once we've identified them we can come up with interventions that mimic caloric restriction."