X-Message-Number: 14408
From: "Gary Tripp" <>
Subject: drug extends life-span by 50% in worms
Date: Sun, 3 Sep 2000 15:56:31 -0400

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 that had a mitochondrial defect
causing increased oxygen radical production and rapid aging. The findings
were reported in the September 1, 2000 issue of Science.
The collaborative research was conducted by Simon Melov, Ph.D., of the Buck
Center for Research in Aging and formerly of the Center for Molecular
Medicine at Emory University; Gordon Lithgow, Ph.D., University of
Manchester, UK; Douglas Wallace, Ph.D., director of the Center for Molecular
Medicine at Emory University; and Susan Doctrow, Ph.D. and Bernard Malfroy,
Ph.D. 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 anti-oxidant effect, the compounds are much
more powerful than simple anti-oxidants 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, Dr. Wallace and his colleagues in Emory's Center for
Molecular Medicine have been studying mitochondria -- the tiny power plants
located in the cytoplasm of cells. Dr. Wallace believes that by
demonstrating the effectiveness of these drugs in slowing the aging process,
this work 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, says Dr. Wallace, oxygen radicals
generated inside the 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. 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," he
explains. "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.

Dr. Wallace believes 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 Emory's Center for Molecular
Medicine.

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