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November 7, 2011

Calorie restriction, the practice of limiting daily food intake, can extend the healthy lifespan of a range of animals. In some studies, animals on restricted diets lived more than twice as long on average as those on non-restricted diets.

Scientists at the Salk Institute for Biological Studies and their collaborators found that tweaking a gene known as PGC-1, which is also found in human DNA, in the intestinal stem cells of fruit flies delayed the aging of their intestine and extended their lifespan by as much as 50 percent.

“Fruit flies and humans have a lot more in common than most people think,” says Leanne Jones, an associate professor in Salk’s Laboratory of Genetics and a lead scientist on the project. “There is a tremendous amount of similarity between a human small intestine and the fruit fly intestine.”

The findings of the study, which was a collaboration between researchers at the Salk Institute for Biological Studies and the University of California, Los Angeles, were published online in Cell Metabolism: A PGC-1 Tale: Healthier Intestinal Stem Cells, Longer Life

While little is known about the biological mechanisms underlying this phenomenon, studies have shown that the cells of calorie-restricted animals have greater numbers of energy-generating structures known as mitochondria. In mammals and flies, the PGC-1 gene regulates the number of these cellular power plants, which convert sugars and fats from food into the energy for cellular functions.

The researchers found that boosting the activity of dPGC-1, the fruit fly version of the gene, resulted in greater numbers of mitochondria and more energy-production in flies – the same phenomenon seen in organisms on calorie restricted diets. When the activity of the gene was accelerated in stem and progenitor cells of the intestine, which serve to replenish intestinal tissues, these cellular changes correspond with better health and longer lifespan. The flies lived between 20 and 50 percent longer, depending on the method and extent to which the activity of the gene was altered.

Part of the reason for this might be that boosting the fruit fly version of PGC-1 stimulates the stem cells that replenish the intestinal tissues, keeping the flies’ intestines healthier. The findings suggest that the fruit fly version of PGC-1 can act as a biological dial for slowing the aging process and might serve as a target for drugs or other therapies to put the breaks on aging and age-related diseases.

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