Emory Report

September 25, 2000

 Volume 53, No.5

Drug 'scrubbers' extend lifespan of worms by half

By Sarah Goodwin

Using drugs that help eliminate oxygen radicals-the toxic byproducts of metabolism-scientists have extended the normal lifespan of the nematode worm C. elegans by approximately 50 percent.

In addition, the scientists restored a normal lifespan to mutant worms with mitochondrial defects that caused increased oxygen radical production and rapid aging. The findings were reported in the Sept.1 issue of Science.

The collaborative research was conducted by Simon Melov of the Buck Center for Research in Aging and formerly of Emory's Center for Molecular Medicine (CMM); Gordon Lithgow, University of Manchester, England; Douglas Wallace, CMM director; and Susan Doctrow and Bernard Malfroy of Eukarion Inc., a biopharmaceutical company.

The drugs used in the experiments are synthetic forms of superoxide dismutase and catalase, enzymes that naturally help control oxidative stress. Although they have an antioxidant effect, the compounds are much more powerful than simple antioxidants such as vitamin E, which eliminate individual oxygen radical molecules one-on-one and quickly lose their effectiveness.

The new synthetic compounds are catalytic drugs that convert oxygen radicals to water, then reconstitute themselves in a cogwheel-like process that continues to destroy additional oxygen radicals as long as the drugs remain in the body.

Since the early 1970s, Wallace and his CMM colleagues have been studying mitochondria-the tiny power plants located in the cytoplasm of cells. Wallace believes that demonstrating the effectiveness of these drugs in slowing the aging process supports his long-held hypothesis that oxygen radicals generated in the mitochondria during metabolism are a major cause of degenerative diseases and aging.

As byproducts of energy generation, Wallace said, oxygen radicals generated inside mitochondria inhibit mitochondrial function and gradually destroy the mitochondrial DNA, which are the blueprints necessary to keep these power plants of the body functioning.

"If you have a power plant that burns coal, you will get energy but also toxic smoke," Wallace said. "You can decrease the toxicity of the smoke by putting a scrubber into the smokestack.

"In this case, we are putting in a catalytic drug which acts like a scrubber to eliminate the oxygen radicals. We believe this protects the mitochondria and the cell from being damaged by the mitochondrial toxic byproducts and allows them to function efficiently for much longer."

Advancing age is a common component of many diseases including Alzheimer's, Parkinson's, diabetes and cardiovascular disease. By affecting the aging process overall, scientists hope they will be able to defer the onset of many age-related disorders.

Wallace said this research opens the door to a wide range of additional drugs that could be developed with similar or even better effects, which will be a major goal of CMM.

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