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Release: Feb. 26, 2002

NOTE TO EDITORS: Dr. Hoshi currently is associate professor of physiology, University of Pennsylvania. He can be reached at (215) 573-7305 or by email at hoshi@hoshi.org

UI-based study finds antioxidant enzyme delays aging in fruit flies

A collaborative study involving University of Iowa researchers has found that an antioxidant enzyme, which repairs cellular damage caused by oxidation, slows the aging process in fruit flies. The enzyme, called peptide methionine sulfoxide reductase A (MSRA), also is found in other species, including humans. The findings, published in the Feb. 26 online issue of the Proceedings of the National Academy of Sciences, could have implications for the study of aging and age-related disease in humans.

Although all the factors involved in aging and age-related disease are not fully understood, oxidative damage of cellular components such as proteins and DNA appears to play a key role. A build-up of damage from oxidation is thought to speed up aging and shorten life.

Organisms that require oxygen use oxidation reaction to metabolize oxygen and produce cellular energy. However, as well as keeping cells and organisms alive, oxidation reactions also produce intermediate reactive oxygen species such as free radicals, which can damage cellular components. Normally, cells have a finely balanced antioxidant system in place to cope with these toxic molecules. MSRA is one such antioxidant. This enzyme repairs a specific type of oxidative damage (the oxidation of methionine residues in proteins).

Previous studies have shown that older rats have less MSRA than young rats and the enzyme is not as active in the older rats. The enzyme also appears to be less active in the brains of patients with Alzheimer's disease. Therefore, MSRA may be an important factor in aging and age-related disease processes.

The UI team found that fruit flies genetically engineered to produce increased amounts of this enzyme, in particular in the flies' nervous system, had significantly increased lifespans. These flies lived around 70 percent longer than normal flies and experiments indicated that the increase was due to a delay in the onset of normal processes that control aging and death.

A longer than average lifespan has been linked to increased resistance to environmental stress such as starvation or oxidative stress. The increased levels of MSRA did appear to specifically protect the fruit flies from oxidative stress induced by the pesticide paraquat, but did not protect the flies from starvation.

"The findings demonstrate that methionine oxidation is important in aging," said Toshinori Hoshi, Ph.D., principal investigator on the study. Hoshi was an associate professor of physiology and biophysics at the UI when the study was conducted. He has since moved to the Department of Physiology at the University of Pennsylvania. The findings show that oxidative damage is an important factor in determining an organism's lifespan.

Although life is extended for fruit flies with increased levels of MSRA, the rate of development for the flies is normal and their behavior and appearance also are completely normal.

Aging in many organisms is associated with a decline in physical activity and in the ability to reproduce. Importantly, the flies that over-produced MSRA were noticeably more active than normal flies of the same age and also were able to maintain their ability to reproduce well into what might be considered old age. At the same time, the altered flies maintain normal food intake and body weight as compared to the control flies.

"The increased lifespan for the flies does not depend on them eating less food or being less active," Hoshi said. "These flies may have a more efficient metabolism.

"They eat the same amount of food, have lots of sex, stay physically active and live longer," Hoshi added.

The findings suggest that increased amounts of the enzyme MSRA extend the flies' lifespan while maintaining quality of life. These results could have implications for aging in humans if the enzyme is found to act in a similar way in humans as it does in fruit flies.

In addition to Hoshi, the research team included the following UI researchers: Hongyu Ruan, graduate student in biological sciences; Xiang Dong Tang, M.D., Ph.D., research associate (now at U. Penn.); M.-L. Chen, Ph.D., formerly a postdoctoral fellow in biological sciences; M. A. Joiner, Ph.D., postdoctoral researcher in biological sciences; and Chun-Fang Wu, Ph.D., professor of biological sciences. The team also included Nathan Brot, Ph.D., and Guangrong Sun, in the Department of Microbiology and Immunology, Weill Medical College, Cornell University; Linda Iverson, Ph.D., associate investigator, Division of Neurosciences, City of Hope Beckman Research Institute, Duarte, California; Herb Weissbach, Ph.D., Distinguished Research Professor and Director, Center for Molecular Biology and Biotechnology, Florida Atlantic University; and Stefan Heinemann, Ph.D., professor, Research Unit Molecular and Cellular Biophysics, Friedrich Schiller University, Jena, Germany.

The study was funded in part by grants from the National Institutes of Health and by the Carver Foundation Collaborative Grant program administered by UI College of Medicine.

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