El intestino de la mosca de la fruta podría guardar el secreto de la fuente de la juventud

El intestino de la mosca de la fruta podría guardar el secreto de la fuente de la juventud

Long-lived fruit flies offer Salk scientists clues to slowing human aging and fighting disease

LA JOLLA, CA—Una de las pocas formas fiables de extender la vida de un organismo, ya sea una mosca de la fruta o un ratón, es restringir la ingesta de calorías. Ahora, un nuevo estudio en moscas de la fruta está ayudando a explicar por qué tales dietas mínimas están relacionadas con la longevidad y ofreciendo pistas sobre los efectos del envejecimiento en el comportamiento de las células madre.

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 Laboratorio de Genética 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 Metabolismo celular.

Scientists have long known that 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.

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 PCG-1 gene regulates the number of these cellular power plants, which convert sugars and fats from food into the energy for cellular functions.

In young fruit flies (left), 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, 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 PCG-1 gene delayed this aging process, while simultaneously extending lifespan.

Image: Courtesy of Salk Institute for Biological Studies

This chain of connections between the mitochondria and longevity inspired Jones and her colleague to investigate what happens when the PCG-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 PCG-1 gene. The flies (known as Drosophila melanogaster) have a short lifespan, allowing the scientists to study aging and longevity in ways that aren’t as feasible in longer-lived organisms such as mice or human.

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.

“Their intestines were beautiful,” says Christopher L. Koehler, a doctoral-student at University of California San Diego who conducts research in Jones’ laboratory. “The flies with the modified gene activity were much more active and robust than the other flies.”

Part of the reason for this might be that boosting the fruit fly version of PCG-1 stimulates the stem cells that replenish the intestinal tissues, keeping the flies’ intestines healthier. The findings suggest that the fruit fly version of PCG-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.

“Slowing the aging of a single, important organ – in this case the intestine – could have a dramatic effect on overall health and longevity,” Jones says. “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 Salk researchers were supported by the Emerald Foundation, the G. Harold and Leila Y. Mathers Charitable Foundation, la American Cancer Society, la California Institute for Regenerative Medicine and the Institutos Nacionales de Salud.

Acerca del Instituto Salk de Estudios Biológicos:
El Instituto Salk de Estudios Biológicos es una de las instituciones de investigación básica más destacadas del mundo, donde un cuerpo docente de prestigio internacional investiga cuestiones fundamentales de las ciencias de la vida en un entorno único, colaborativo y creativo. Centrados tanto en el descubrimiento como en la formación de las futuras generaciones de investigadores, los científicos del Salk realizan contribuciones revolucionarias a nuestra comprensión del cáncer, el envejecimiento, el Alzheimer, la diabetes y las enfermedades infecciosas mediante el estudio de la neurociencia, la genética, la biología celular y vegetal, y otras disciplinas relacionadas.

Los logros del cuerpo docente han sido reconocidos con numerosos galardones, entre los que se incluyen premios Nobel y la pertenencia a la Academia Nacional de Ciencias. Fundado en 1960 por el Dr. Jonas Salk, pionero en la vacuna contra la poliomielitis, el Instituto es una organización independiente sin fines de lucro y un hito arquitectónico.