Science / Medicine : IS IT THE DEATH OF US? : OXYGEN : New light on the ‘free radicals’ that cause aging.
When Prometheus stole the flame of eternal life, the enraged Gods banished him from Olympus. This robbed him of immortality and condemned humanity to death. Now scientists on the cutting edge of longevity research have discovered that the spiritual duality that inspired this Greek myth--the sustaining life force is ultimately lethal--is rooted in reality. When we breathe oxygen, it creates highly reactive free radical molecules that go on a deadly rampage throughout our bodies.
“This is the ultimate paradox: oxygen is essential for life yet it forms substances that may be killing us,” says Paul Hochstein, director of the Institute for Toxicology at the USC School of Pharmacy. The Institute, which was founded in 1980, is one of the few centers in the world devoted solely to the study of free radicals.
What scientists are learning here and at other research facilities about free radicals sheds new light on the understanding of the mechanisms of aging, and about many of the debilitating illnesses that accompany aging. This knowledge may eventually yield therapies to maximize lifespan and to maintain full mental and physical capabilities well into old age, according to some researchers.
Free radical reactions contribute directly to the physical ravages of age. The oxidative damage caused by free radicals “rusts” cells in much the same way as oxygen erodes metal, and gradually wears down our bodily organs. These volatile molecules may even be the key agents in hastening aging because they break down or alter DNA, the master regulator of the cell.
This also upsets the body’s delicate chemical balance and weakens our immune system so that we are more susceptible to disease. Free radicals are believed to play a major role in causing or aggravating more than 60 of the afflictions associated with aging, including cancer, heart disease, high blood pressure, rheumatoid arthritis, cataracts, glaucoma, emphysema, Parkinson’s disease and stroke.
Free radicals are a by-product of our normal metabolism, though some are created by radiation, ozone exposure, cancer-causing chemicals and other environmental toxins. These free radicals form briefly when oxygen courses through the body and has a chemical reaction with the cells. Free radicals cruise through our bodies searching for an electron mate, like heat-seeking missiles. When they link up with another molecule, that molecule suddenly has an extra electron. To restore its electrical balance, the molecule latches onto yet another molecule. This process triggers a toxic chain reaction that wreaks havoc at that site in the body. Cells are destroyed or severely damaged, and genes are chewed up or reprogrammed.
Pioneering scientists are now looking for ways to delay, prevent or even reverse the physical deterioration that’s triggered by these renegade molecules. For example, Kelvin Davies, an associate professor at USC and a member of the faculty at the Institute, believes that eventually we will be able to mobilize the body’s natural defenses to halt the degeneration triggered by free radicals.
The British-born biochemist has discovered a class of enzymes that are programmed to repair damage caused by free radical reactions. Davies postulated the existence of genes that coded for these enzymes based on his observation of oxidative damage to cell cultures bombarded with hydrogen peroxide (an unstable oxygen molecule). “We hit these cells with lethal doses of hydrogen peroxide but it didn’t kill them off. So the cells must have some way of removing or repairing damage.”
It turned out they do. Some of the body’s enzymes function as a repair system to fix the damage done by free radicals. Davies discovered one set of enzymes, macroxyprotheinase (MOP), salvages injured proteins. Another class of enzymes, phopholipases, performs a similar function with cell membranes, while yet a third group, nucleases and glycosylases, actually repair the DNA. Initially, cells are able to combat this bombardment. “But the cumulative effects of this damage over time may diminish the cell’s ability to make these repairs,” says Davies. “This may be what causes some of the physical degeneration of aging.” In other words, our bodies are ground down from wear and tear, and all the debris that collects in our system.
This discovery provides some intriguing clues into the aging process: it may be that the reason some people live to a vital old age is because their internal salvage system retains its vigor.
Researchers are also investigating the role free radicals play in disturbing the normal regulatory function of the DNA. Some researchers have found free radicals do damage to the DNA, which inhibits the production of the enzyme Adenosine Triphosphate (ATP). This enzyme provides fuel for cellular activity. The DNA damage also triggers the activation of an enzyme--Poly-ADP Rebose Polymerase--that might enhance the formation of malignant tumors in cells.
Scientists have also uncovered a number of natural substances that counteract the damage spawned by free radical reactions. The food preservative BHT, and common nutrients like selenium, vitamins, A, C, and E, and beta-carotene, have been shown to be antioxidants; anti-oxidants disarm free radicals by scooping-up their extra electrons before renegade molecules can cause trouble. Our bodies also produce enzymes, like superoxide dismutase (SOD), catalase, gluthathione peroxidase and DT diaphrorase, that neutralize free radicals by converting them to harmless chemicals.
Studies are now in progress to test the disease-fighting potential of these free radical inhibitors. The National Institute of Neurological and Communicative Disorders and Stroke, for instance, has funded a $10-million study to see if vitamin E and deprenyl, a drug that inhibits the formation of free radicals, can stem the loss of brain cells in 800 patients who are in the early stages of Parkinson’s disease. “Based upon previous data,” explains Gerald Cohen, a professor of neurology at the Mt. Sinai School of Medicine in New York and a member of the scientific advisory committee for the Parkinson’s study, “these two agents used in combination hold out the promise of stopping the progression of this crippling disorder.”
Free radical research is also broadening scientists’ comprehension of the link between cholesterol--specifically, the “bad” cholesterol known as low density lipoprotein (LDL)--and another major killer, atherosclerosis. “Studies show that if LDL is modified by free radicals--forming a toxic substance called cholesterol epoxide--this altered LDL is much more readily deposited in the cell walls,” explains Alex Sevanian, an associate professor at USC and a member of the faculty at the Institute. “The accumulation of these fat-filled cells in the walls of the arteries is one of the hallmarks of the early stages of atherosclerosis.”
In a recent experiment that Sevanian conducted in tandem with Judy Berliner, a biochemist at UCLA, LDL was deliberately enriched with cholesterol apoxide. Sure enough, the transformed LDL penetrated cell membranes like a knife slicing through warm butter. “The cause-effect relationship is very compelling,” says Sevanian. “This free radical reaction may be pivotal in causing atherosclerosis, as well as increasing the risk of high blood pressure.”
Free radicals may also be the culprits behind much of the damage that accompanies heart attacks and strokes. Numerous studies reveal that when blood flow to the heart--or to other vital organs like the brain, lungs and kidneys--is temporarily stopped, the real destruction occurs after the blood flow has been resumed. That’s because the rush of oxygen fuels the formation of free radicals.
Hochstein and his colleagues have found that when oxygen flow is restored to the heart, the free radicals transform oxygen into hydrogen peroxide. Then the hydrogen peroxide converts myoglobin--which normally transports oxygen to the muscles--into a “toxic enzyme-like substance that damages the heart,” explains Hochstein. “Not all the damage sustained during a heart attack can be attributed to free radical reactions. But they are a key element.”
Researchers are monitoring the effectiveness of antioxidants such as beta-carotene and vitamins A, C, and E to combat cancer. “We found that smokers who eat leafy green vegetables”--which are rich in vitamin A and C--”develop lung cancer less often than those who don’t,” says William Pryor, a professor of biochemistry at Louisiana State University in Baton Rouge and a pioneer in the study of free radicals. “It’s conceivable smokers could benefit from an antioxidant supplementation regimen.”
Other scientists are investigating the therapeutic possibilities of using vitamin C to reverse the damage by sunlight and oxygen that makes our eyes more vulnerable to the formation of cataracts. And still others are employing antiradical agents to halt the neurological damage triggered by oxygen radicals after strokes or injuries to the head and spinal cord, and to curb tissue damage in such diseases as emphysema.
“There’s been a renaissance in free radical biology in the past decade,” says Pryor. “Within the next 10 or so years, (we) will promote a modest extension in lifespan--perhaps five to eight years.”
The “ Free Radical “ 1. Oxygen molecules enter the body through eating or breathing. 2. In normal metabolism, molecule becomes unstable by losing one of its electrons to another molecule. Unstable molecule known as “free radical.” 3. “Free radical” latches onto another molecule in the membrane of a cell. Molecule travels off and leaves cell with its own “free radical.” 4. After cell membrane has been broken by the chain of “free radical” exchanges, cell begins to disintegrate. This damages the genes and can destroy the cell.
