Inside Salk; Salk Institute
Home > News & Press > InsideSalk > 03|12 Issue > Fruit fly intestine may hold secret to the fountain of youth –

Fruit fly intestine may hold secret to the fountain of youth

Conrad Prebys

In young fruit flies (top), the intestinal tissues are highly organized, as shown by the even distribution of different cell types, each represented by a different color. As flies age, this order breaks down (bottom), caused by unregulated stem cell activity and inability to form cells with specialized functions. The Salk scientists and their collaborators discovered that activating the fruit fly version of the PGC-1 gene delayed this aging process, while simultaneously extending lifespan.

Image courtesy of Salk Institute for Biological Studies

Scientists have long known that calorie restriction 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 unrestricted diets. 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 connections between mitochondria and longevity inspired Leanne Jones and her colleagues to investigate what happens when the PGC-1 gene is forced into overdrive. To do this, they used genetic engineering techniques to boost the activity of the fruit fly equivalent of the PGC-1 gene, called dPGC-1. They found that increasing its activity 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 produced better health and longer lifespans. The flies lived between 20 and 50 percent longer, depending on the method and extent to which the activity of the gene was altered, and the flies with the modified gene activity were much more active and robust than the control flies.

Part of the reason might be that boosting the fruit fly version of PGC-1 delays the aging of stem cells that replenish the intestinal tissues, keeping the flies' intestines healthier for longer. The findings, reported in Cell Metabolism, 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.