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from the issue of December 2, 2004
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Redox Biology event addresses oxygen, aging
Symposium discusses: Are we rusting?
BY JULIE M. STONE, SPECIAL TO THE SCARLET
Oxygen is both friend and foe. It is required for engine combustion to run an automobile, yet oxygen reacts with exposed metal on the car body, forming rust and eventually destroying the vehicle.
Similarly, the human body needs oxygen for a wide range of biological processes, yet oxygen by-products, if left unchecked, can damage cellular proteins, membranes and nucleic acids.
This damage - like a biological version of body rust - has long been thought to contribute to the ravages of aging. To explore this and other issues related to aging, more than 150 people attended the Nebraska Redox Biology Center's second annual minisymposium, "The Redox Biology of Aging," on Oct. 1 at the Nebraska Union.
The symposium focused on the biochemistry of aging and its relationships to longevity and age-related diseases. Experts from eight universities or institutes described their research using a wide variety of experimental approaches - from structural studies of individual molecules to aging of whole organisms. These authorities confirmed that both mortality and many age-related neurodegenerative diseases are linked to "redox" reactions.
"Redox" is short for chemical reactions involving reduction and oxidation. In redox reactions, electrons from one molecule (or atom) move to another. The molecule that receives one or more electrons is reduced, while the molecule that gives up the electrons is oxidized.
Electrons generally like to be in pairs, and when unpaired (as in so-called "free radicals"), they become unstable and potentially dangerous. Free radicals can react with other molecules and cause destructive chain reactions. Normally, healthy cells can protect themselves from these harmful molecules. But the inability to cope with these reactive molecules can cause many age-related diseases.
Free radicals form in response to environmental pollutants, but are also formed during normal processes such as metabolism and respiration. Antioxidants, such as some vitamins, can react with or scavenge harmful free radicals to prevent cellular damage. That's why taking these antioxidants has been touted to increase life span.
Verifying these claims has been difficult in humans, but four of the eight scientists at the symposium reported on rigorous tests of these claims in so-called model systems - organisms that can be easily manipulated in the laboratory and whose DNA sequence (genome) is known. Four researchers reported that in three model systems - baker's yeast, a nematode worm and the fruit fly - restricting calories extends lifespan. This effect is attributed to "hormesis," the fact that a little bit of stress, such as starvation, can be beneficial by provoking a defense response.
"Anything that doesn't kill you will probably make you live longer," said David Sinclair of Harvard Medical School, one of the researchers in this project. The other three are Thomas Johnson of the University of Colorado, Vadim Gladyshev of UNL and John Tower of the University of Southern California. All four scientists pinpointed antioxidant enzymes as major contributors to longevity.
The other four speakers discussed the molecular basis underlying age-related diseases such as Parkinson's, Alzheimer's and Lou Gehrig's disease. While these diseases are distinctly different, they all share a link to redox. Misregulation of proteins containing metals, such as copper, zinc and iron, correlates with development of these diseases. Therefore, these diseases do appear to resemble a biological form of rusting. These four speakers were Gregory Petsko of Brandeis University, Julie Andersen of the Buck Institute for Age Research, Ashley Bush of Massachusetts General Hospital and Joan Valentine of the University of California, Los Angeles.
The symposium marked the 50th anniversary of the concept of the "Free Radical Theory of Aging." This theory, proposed by Denham Harman, emeritus professor of medicine at the University of Nebraska Medical Center, led to more than 50 research papers supporting his belief that a healthy lifestyle and antioxidant supplements can reduce the consequences of aging. At almost 90 years old, Harman is officially retired but still works at UNMC.
Julie M. Stone is an assistant professor of biochemistry at UNL.
GO TO: ISSUE OF DECEMBER 2
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Symposium discusses: Are we rusting?
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