No 12, October 29, 2002
A Protein as Fountain of Youth?
Clinical Researchers Detect Function of Protein INDY
Caloric restriction is the only known means of extending life
span in mammals, including humans. This is also the case for the fruit fly
Drosophila. Although the mechanism by which caloric restriction extends life
span is not yet understood, researchers assume that it is likely to include
alterations in energy utilization. Two years ago, Blanka Rogina and Stephen L.
Helfand from the University of Connecticut Health Center (Farmington/USA)
discovered a gene, which doubles the average life span of fruit flies when
mutated without a loss of fertility or physical activity. The analyses of data
from gene banks gave them the hint, that the gene might be involved in energy
balancing. Therefore, they named the gene „I am not dead yet“ (Indy), which is
somewhat macabre. Now Felix Knauf from the Franz Volhard Clinic for
Cardiovascular Diseases (Charité, Medical School of Humboldt-University of Berlin/Helios
Kliniken) and the Max Delbrück Center for Molecular Medicine (MDC) Berlin-Buch
in Germany and Stephen L. Helfand have been able to detect the function of
Indy. Together with Peter S. Aronson from Yale University (New Haven,
Connecticut/USA) and Blanka Rogina they were able to demonstrate that Indy`s
product, the protein INDY, functions as a transporter of nutrients important
for normal metabolism. Their
research has now been published in the renowned American Journal Proceedings of
the
Earlier, studies by the group of Stephen L. Helfand from the University of Connecticut have shown, that INDY is active especially in those cells and organs that play a major role in the uptake, utilization and energy storage of nutrients. These tissues include cells of the digestive system and of the fat body of the fruit fly, an organ which is similar to the liver of humans. While working with Peter S. Aronson at Yale University in New Haven, USA, Felix Knauf expressed the protein INDY in oocytes of the Xenopus, which is a model organism in biology. He continued these studies in Berlin/Germany at the Franz Volhard Clinic and the MDC and demonstrated that INDY transports metabolites, especially intermediate metabolites of the Krebs cycle. The Krebs cycle plays an important role in metabolism. It yields energy from carbohydrates, fat and protein. It is named after its discoverer Nobel Laureate Sir Hans Adolf Krebs.
„Genetic diet“
Together with his colleague Blanka Rogina Felix Knauf was able to show that INDY is expressed in the plasma membranes of cells of the digestive system and the membranes of other organs involved in metabolism. Those flies who lived longer than the others, had a decrease in INDY-protein. Therefore there was a gap in the transport and metabolism of nutrients. As a result it is thought that the flies „enjoy a genetic diet”. Similar proteins are found in humans. „Given the universal role of energy balance in aging genetic or pharmacological manipulation of functionally analogous transporters may provide a rational approach for extending healthy life in a variety of species, including humans“, the researchers dream.
*Functional
characterization and immunolocalization of the transporter encoded by the
life-extending gene Indy Felix Knauf1,2, Blanka Rogina3, Zhirong Jiang1,
Peter S. Aronson1, and Stephen L. Helfand3 1Department
of Internal Medicine, Yale University School of Medicine, New Haven, CT 06520; 2Franz
Volhard Clinic/Helios Kliniken Berlin, Medical Faculty Charité and Max Delbrück
Center, and 3Department of Genetics and Developmental Biology,
School of Medicine, University of Connecticut Health Center, Farmington, CT
06030
Barbara Bachtler
Press and Public Affairs
Max Delbrück Center for Molecular Medicine (MDC) Berlin-Buch
Robert-Rössle-Straße 10; 13125 Berlin; Germany
Phone: +49 (0) 30 94 06 - 38 96
Fax: +49 (0) 30 94 06 - 38 33
e-mail: presse@mdc-berlin.de
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