Monday, September 8, 1997
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Section: Health
Page: S-8

Are Experts Closing In on the Fountains of Youth?;

By: THOMAS H. MAUGH II
TIMES MEDICAL WRITER



Gerontologists, those scientists whose specialty is the study of aging, have been trying to puzzle out the mysteries of aging throughout the latter half of this century. Aside from normal wear and tear, they have identified three primary mechanisms--one genetic and two chemical--that lead to the body's breakdown.
Genetically, the cells that compose us seem programmed to have a finite life span. In the early 1950s, Leonard Hayflick of UC San Francisco discovered that all cells, whether from humans or worms, are able to reproduce themselves only a certain number of times. After that, their metabolic functions begin to deteriorate, their membranes weaken, and they--and, eventually, we--die.
Researchers still don't know what drives this cellular timetable. But until they can find a way to overcome it, the lives of humans seem to be capped at about 120 years.
Unfortunately, two types of chemical reactions conspire to reduce actual life span well below that theoretical limit, to the current average age of 76.

The first is called free-radical oxidation. Like an electric power plant or an automobile engine, the body produces waste products as it burns its fuel (food) for energy. These wastes are called oxygen free radicals--highly reactive oxygen molecules that bond with virtually any biological substances they come into contact with.

When free radicals bind to proteins and membranes, they weaken tissues and internal organs. When they bind to DNA--the genetic blueprint of life--they can produce cancer-causing mutations. The body has repair mechanisms that can reverse some or all of this damage, but as the body ages, those mechanisms become less effective.

The second destructive mechanism is called glycosylation, a process whereby sugars in the blood stream bind to proteins in a manner almost identical to the browning that occurs in cooking.

As glycosylation continues over time, the buildup of sugars on the surface of proteins causes them to stick together and bind to places in the cell where they normally wouldn't. This can stiffen joints, block arteries and cloud clear tissues, such as the lenses of the eyes, leading to cataracts.

Glycosylation is a newly recognized process originally associated with diabetes, but researchers are becoming convinced that it also plays a major role in normal aging and hope to develop drugs to block it.

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Despite years of research, scientists have identified only two treatments that extend life without being aimed at specific diseases: caloric restriction and hormone replacement therapy.

Gerontologists have demonstrated in rats, mice, spiders, fleas, fruit flies, hamsters and fish, among others, that reducing food consumption by about 30% below normal levels, while maintaining adequate levels of vitamins, trace metals and so forth, can lead to a 40% to 50% increase in life span. More recently, gerontologist George Roth and his colleagues at the National Institute on Aging's Gerontology Research Center in Baltimore have shown a similar prolongation of life in rhesus and squirrel monkeys.

Most people believe that the effects of the diet arise from decreased production of free radicals because less food is being burned in the cell's furnaces. Body temperature is also reduced by a degree or so, which further reduces free radical production.

But maintaining such a regimen requires a massive exercise of willpower that is probably beyond the reach of most mortals.

"Most people don't want to go on a diet, much less one that requires a 30% reduction in calories," Roth said. Eventually, however, "what we would optimally seek is a drug that would allow you to eat any of the foods you want, but enable you to still get the beneficial effects of caloric restriction."

That's probably 20 years away at least.

Hormone replacement therapy, in contrast, is much easier and, in terms of quality of life, much more beneficial. When women pass through menopause, their bodies stop producing as much estrogen as they did earlier in life. Although this is seemingly a natural process, a broad spectrum of studies has demonstrated that reduced estrogen levels leave women at greatly increased risk for osteoporosis, heart disease, Alzheimer's disease and a variety of other conditions.

Several recent studies have shown that hormone replacement therapy can prevent these problems, as well as stave off colon cancer, reduce wrinkling and keep teeth sound.

On average, hormone replacement therapy increases life expectancy by about eight years, with the greatest benefits among women who have one or more risk factors for heart disease, such as high cholesterol, high blood pressure and obesity. If ever there was a wonder drug, this is it.

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Estrogens are not for all women, however. Those with a family history of breast or ovarian cancer increase their risk by taking hormones. In other women, as well, prolonged hormone replacement therapy can raise the risk of breast cancer, but the decreased risk of heart disease generally outweighs that risk. Despite most women's fear of breast cancer, a woman is seven times as likely to die of heart disease as of breast cancer.

Here too the chemists are working away. New studies show that synthetic hormones such as tamoxifen and raloxifene provide the protective effects of estrogen in women without increasing the risk of cancer.

Surprisingly, the drug benefits men as well, though it's a select group.

Studies in males taking estrogen as a prelude to sex-change surgery show a sharply reduced risk of heart disease. For most men, however, the feminizing effects--such as increased breast size--outweigh the potential benefits. Researchers are hard at work testing so-called designer estrogens that provide the beneficial effects of the hormone without disturbing male hormones.




Descriptors: AGING; LONGEVITY; MEDICAL RESEARCH;

Copyright (c) 1997 Times Mirror Company

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