Scientists rethinking what makes us get old

McClatchy NewspapersNovember 13, 2008 

US NEWS SCI-AGING MCT

These before-and-after photos show how oxidative stress produced by the buildup of "free radicals"-defective oxygen molecules- damages brain cells. Such damage accumulates as a person ages and causes diseases like Alzheimers, cancer and ultimately death.

DR. AZAD BONNI — Dr. Azad Bonni / Harvard Medical School / MCT

WASHINGTON — Growing old isn't for sissies, the saying goes. The passage of years usually brings physical frailty, failing memory, cancer and other diseases.

As more people live longer, scientists are stepping up their efforts to understand the biological process of aging. Recent research is changing their views on how and why we age.

For half a century, much of the deterioration that comes over time has been blamed on "free radicals.'' These aren't 1960s-style bomb throwers, but toxic, unstable molecules of oxygen running amok in the cells of your body.

This is sometimes called the "oxygen paradox,'' since oxygen is both necessary for — and dangerous to — living organisms.

"Oxygen is both friend and foe,'' said Bennett Van Houten, a molecular biologist at the University of Pittsburgh Cancer Institute.

A free-radical molecule consists of two linked atoms of oxygen with an odd number of electrons in its system, not the even number that the laws of chemistry require.

That chemical oddity drives a free radical to steal an electron from a neighboring oxygen molecule. Now the next molecule has the same problem, setting off a chain reaction that can damage DNA and other cell structures.

As the damage piles up over the years, it leads to increasing disability and ultimately is a common cause of death.

Free radicals frequently are created in special structures called mitochondria. These are little factories inside cells that burn oxygen to manufacture packets of energy in a form your body can use.

Unfortunately, the oxidation process produces as many as 10,000 free radicals in a cell each day, according to Bruce Ames, a molecular biologist at the University of California, Berkeley.

Natural "antioxidants'' in vitamins, fruits and vegetables get rid of most of these harmful molecules, but a few are left to carry on their rampages.

"Aging is caused by the gradual, lifelong accumulation of a wide variety of molecular and cellular damage,'' said Tom Kirkwood, of the Newcastle University Institute for Ageing and Health, in Newcastle, England.

Views on the central role of free radicals are changing as new research reveals a more complex picture. Genes, environment, nutrition and lifestyle also are recognized as parts of a complex web of factors that cause aging.

Ultraviolet radiation from the sun, toxic chemicals, tobacco smoke or chance accidents that happen when cells divide can create free radicals. The result is what scientists call "oxidative stress,'' a major cause of cancer, Alzheimer's and heart disease.

A conference of world experts on "Oxidative Stress and Disease'' in Italy next March will review whether the free radical theory needs updating.

"The free radical theory is the most widely accepted theory of aging,'' said Pittsburgh's Van Houten, who'll lead a panel at the conference. "But the idea that aging is caused by one thing is naive. One general theory can never fit all.''

"Clearly, it's the combination of genes that your parents dealt you and the lifestyle choices you make and the environmental toxins one is exposed to,'' he explained.

"One need only count the number of ways a car will fail to start to appreciate that aging can be caused by a large number of problems. Like any machine, it's going to wear out.''

According to Kirkwood, about 25 percent of how a person ages is due to inherited genes. Certain genes control a cell's ability to repair damaged DNA. If those genes are defective, they can't do their job.

Another panelist at the March conference, Holly Van Remmen, a leading researcher on aging at the University of Texas Health Science Center in San Antonio, measured oxidative stress under a grant from the National Institute of Aging in Bethesda, Md.

"Not everybody will be susceptible to diseases like Parkinson's or cancer as they age,'' Van Remmen said in a lecture last fall. "But each one of us will lose muscle mass and muscle strength. That's why this research is so important. Frailty affects all of us.''

Extra antioxidants, such as high doses of vitamins C and E, sometimes are prescribed to deal with oxidative stress by mopping up free radicals. Their effectiveness, however, has been unclear, and excessive use could be harmful.

"Any benefits from antioxidants are likely to be only partial,'' Kirkwood said. "Merely throwing in some extra molecules of one or another antioxidant might as easily do harm as good.''

"To naively take large doses of vitamin C or E is ridiculous; not a good idea,'' Van Houten agreed.

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