Gene tweak that extends lifespan of fruit flies could help slow human aging

Caloric restriction has been shown to slow the signs of aging and delay the development of age-related diseases in a wide range of animals. However, scientists have been unable to explain just why limiting daily food intake has such a beneficial effect on health and the biological mechanisms that underlie the phenomenon. Researchers in Sweden recently claimed to have unlocked a piece of the puzzle by identifying one of the enzymes that appears to play a major role in the process and now another group in the U.S. has provided another clue by tweaking a gene in fruit flies and extending their lifespan by as much as 50 percent.

While initial results are positive, due to the long lifespan of the species, studies on whether caloric intake works in nonhuman primates and humans are ongoing. Fruit flies, on the other hand, have a much shorter lifespan, with the ability to develop from egg to an adult in as little as seven days. This, along with numerous other reasons, has seen the fruit fly become a model organism that is widely used in studies of genetics and physiology.

A team consisting of researchers from the Salk Institute for Biological Studies and the University of California, Los Angeles, took the fruit fly ( (Drosophila melanogaster) and tweaked a gene in their intestinal stem cells known as dPGC-1, which is also found in human DNA and known as PGC-1. This resulted in the aging of the fruit flies' intestines being delayed and their lifespan being extended by as much as 50 percent.

In flies and mammals, the PGC-1 gene regulates the number of mitochondria within an animal's cells. Mitochondria are often referred to as "cellular power plants" because they convert sugars and fats from food into the energy for cellular functions. Since previous studies had shown that calorie-restricted animals have greater numbers of mitochondria in their cells, the researchers set about investigating what would happen when the PGC-1 is forced into overdrive.

Using genetic engineering techniques to boost the fruit fly equivalent of the PGC-1 gene resulted in the same kind of effects seen in organisms on calorie restricted diets - namely, greater numbers of mitochondria and more energy production. When the activity of the gene was accelerated in stem and progenitor cells of the flies' intestine, which serve to replenish intestinal tissues, these cellular changes corresponded with better health and longer lifespan.

Depending on the method and extent to which the activity of the gene was altered, the flies lived between 20 and 50 percent longer than normal.

The researchers say their 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 brakes on aging and age-related diseases. They theorize that boosting dPGC-1 stimulates the stem cells that replenish the intestinal tissues, thus keeping the flies' intestines healthier.

"Slowing the aging of a single, important organ - in this case the intestine - could have a dramatic effect on overall health and longevity," says Leanne Jones, an associate professor in Salk's Laboratory of Genetics and a lead scientist on the project. "In a disease that affects multiple tissues, for instance, you might focus on keeping one organ healthy, and to do that you might be able to utilize PGC-1."

The findings of the collaboration between the Salk Institute for Biological Studies and University of California, Los Angeles, researchers were published last month in Cell Metabolism.